Tutorial:The opioid receptor, a molecular switch - Revision history

Karsten Theis at 22:00, 9 July 2023

2023-07-09T22:00:06Z

←Older revision		Revision as of 22:00, 9 July 2023
Line 74:		Line 74:
	In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> set refreshing false; load $oxycodone; background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG"; select _C; color mediumpurple; hide _H; moveto 1.0 { -977 204 68 164.66} 5.0 -34.67 36.52 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0; set zshade on; set zshadepower 1; set spinY 0; set spinX 90; spin on;</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>set refreshing false; load $heroin; background image "http://proteopedia.org/wiki/images/e/e6/OpioidFatality3.JPG"; select _C; color orange; hide _H; set zshade on; set zshadepower 1; moveto 1.0 { 970 216 -113 30.11} 5.0 -8.1 36.32 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { 997 68 23 122.37} 42.42 3.87 -19.17 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>set refreshing false; load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1; background image "http://proteopedia.org/wiki/images/5/51/OpioidFatality4.JPG"; moveto 1.0 { 802 6 -597 24.36} 5.1 32.85 34.38 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0;; set refreshing true; moveto 1.0 { -997 -67 -31 130.64} 55.02 -9.39 -19.75 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>fentanyl</text></jmolLink></jmol>.		In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> set refreshing false; load $oxycodone; background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG"; select _C; color mediumpurple; hide _H; moveto 1.0 { -977 204 68 164.66} 5.0 -34.67 36.52 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0; set zshade on; set zshadepower 1; set spinY 0; set spinX 90; spin on;</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>set refreshing false; load $heroin; background image "http://proteopedia.org/wiki/images/e/e6/OpioidFatality3.JPG"; select _C; color orange; hide _H; set zshade on; set zshadepower 1; moveto 1.0 { 970 216 -113 30.11} 5.0 -8.1 36.32 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { 997 68 23 122.37} 42.42 3.87 -19.17 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>set refreshing false; load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1; background image "http://proteopedia.org/wiki/images/5/51/OpioidFatality4.JPG"; moveto 1.0 { 802 6 -597 24.36} 5.1 32.85 34.38 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0;; set refreshing true; moveto 1.0 { -997 -67 -31 130.64} 55.02 -9.39 -19.75 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>fentanyl</text></jmolLink></jmol>.

-	To explore how naloxone reverses an overdose, let's look at the situation during an overdose. The opioid receptor binding pocket is occupied by <scene name='83/830406/Competition/1'>the opioid agonist</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]	+	To explore how naloxone reverses an overdose, let's look at the situation during an overdose. The opioid receptor binding pocket is occupied by <scene name='83/830406/Competition/2'>the opioid agonist</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]
	ago1 = [ {-28.15225471470447 -16.732834272032683 -19.877771911210033},{-27.699108229899412 -15.289706379445466 -19.75851945234414},{-26.68480597889424 -16.41202791313621 -19.553508919395476},{-26.088235349655854 -16.524656204830176 -18.11797335653394},{-26.09670821218129 -17.86095364239696 -17.47014979339886},{-25.422698574661922 -17.721641670729095 -16.199593937451922},{-25.353924216489737 -19.013933850033702 -15.411718940408532},{-26.803804141690954 -19.477321003972328 -15.178642669494419},{-27.445395730810528 -18.494213544008844 -14.383647100365163},{-26.818636191572715 -20.537559246853444 -14.291420105179995},{-26.27682344603074 -19.760003263026004 -13.14885472815232},{-27.207435082797755 -18.77153045507903 -13.06873301160048},{-27.480530055558386 -17.69570033702936 -12.353598273980962},{-27.244161412119684 -17.860947196252614 -11.025351181036363},{-28.364696788636234 -16.68825679789819 -12.736096252513157},{-28.711030406563342 -16.531400987159827 -14.066644365033392},{-28.151812675248582 -17.470874662546446 -14.908529596070698},{-28.472248612776976 -17.533960092984973 -16.285274684460944},{-27.462151991406987 -18.37594262285864 -17.143213047564316},{-27.524423894082027 -19.730606208555294 -16.490990861706834},{-26.83847374040866 -20.703170645740975 -17.280056639824984},{-28.958513651925706 -20.17265541019972 -16.19507859468611},{-28.992617235384415 -21.42435546162589 -15.35837319440775},{-28.25116136928705 -21.038824300654305 -14.024697475745336},{-28.19935710109749 -22.168541971976264 -13.079524845534207},{-29.32189117303061 -22.73375369850398 -12.596195804874707},{-30.46083909789644 -22.348636080546093 -12.857454383264495},{-29.114561027297814 -23.897271044635005 -11.626157869573909},{-30.33443496035501 -24.825982830819825 -11.746855863131952},{-30.532177135749723 -25.36260046177555 -13.177744241104742},{-31.66401160803267 -25.612658051750717 -13.595648451478052},{-29.401879118904926 -25.52914420794582 -13.91816207836175},{-29.753259103332216 -26.02310392303815 -15.217442227678971} ]		ago1 = [ {-28.15225471470447 -16.732834272032683 -19.877771911210033},{-27.699108229899412 -15.289706379445466 -19.75851945234414},{-26.68480597889424 -16.41202791313621 -19.553508919395476},{-26.088235349655854 -16.524656204830176 -18.11797335653394},{-26.09670821218129 -17.86095364239696 -17.47014979339886},{-25.422698574661922 -17.721641670729095 -16.199593937451922},{-25.353924216489737 -19.013933850033702 -15.411718940408532},{-26.803804141690954 -19.477321003972328 -15.178642669494419},{-27.445395730810528 -18.494213544008844 -14.383647100365163},{-26.818636191572715 -20.537559246853444 -14.291420105179995},{-26.27682344603074 -19.760003263026004 -13.14885472815232},{-27.207435082797755 -18.77153045507903 -13.06873301160048},{-27.480530055558386 -17.69570033702936 -12.353598273980962},{-27.244161412119684 -17.860947196252614 -11.025351181036363},{-28.364696788636234 -16.68825679789819 -12.736096252513157},{-28.711030406563342 -16.531400987159827 -14.066644365033392},{-28.151812675248582 -17.470874662546446 -14.908529596070698},{-28.472248612776976 -17.533960092984973 -16.285274684460944},{-27.462151991406987 -18.37594262285864 -17.143213047564316},{-27.524423894082027 -19.730606208555294 -16.490990861706834},{-26.83847374040866 -20.703170645740975 -17.280056639824984},{-28.958513651925706 -20.17265541019972 -16.19507859468611},{-28.992617235384415 -21.42435546162589 -15.35837319440775},{-28.25116136928705 -21.038824300654305 -14.024697475745336},{-28.19935710109749 -22.168541971976264 -13.079524845534207},{-29.32189117303061 -22.73375369850398 -12.596195804874707},{-30.46083909789644 -22.348636080546093 -12.857454383264495},{-29.114561027297814 -23.897271044635005 -11.626157869573909},{-30.33443496035501 -24.825982830819825 -11.746855863131952},{-30.532177135749723 -25.36260046177555 -13.177744241104742},{-31.66401160803267 -25.612658051750717 -13.595648451478052},{-29.401879118904926 -25.52914420794582 -13.91816207836175},{-29.753259103332216 -26.02310392303815 -15.217442227678971} ]
	ago2 = [ {-34.26386300135435 -32.998407428317655 -22.075040189835274},{-33.767972005394476 -31.785329790003857 -22.839707283117654},{-32.81949446748223 -32.50861138609696 -21.886975372856973},{-32.35656815162927 -31.686026101800934 -20.646654174074015},{-32.47337487759003 -32.32592942722871 -19.311619371952094},{-31.909159051353825 -31.40751839168098 -18.34923136745037},{-31.95973567715373 -31.923733461475216 -16.925693518764934},{-33.4412224403542 -32.17676717971283 -16.590469850303663},{-34.11221904893955 -30.92900307598431 -16.645299520315255},{-33.57487543154809 -32.45184072304114 -15.2421522231454},{-33.10647751293254 -31.118043986270415 -14.789162538035006},{-34.00192443298045 -30.31933222157224 -15.429295594757907},{-34.295534080630205 -29.039691289330616 -15.569728708156578},{-34.183700632061864 -28.334200342225728 -14.413358177861756},{-35.10323791540406 -28.51359767071855 -16.576623945878502},{-35.32464590971701 -29.22984459328295 -17.73975671816693},{-34.72983387573878 -30.474848641138685 -17.756175154681134},{-34.929828129067715 -31.39106893129418 -18.815716885120633},{-33.88107103855785 -32.55859275560962 -18.863515261255557},{-34.05251987303332 -33.21145171171779 -17.518611740334293},{-33.33748856327233 -34.44616521213911 -17.461631059934426},{-35.52301088127194 -33.4082201330449 -17.146424444664728},{-35.67873675808378 -33.864851905275984 -15.719809964197012},{-35.04350716039007 -32.713035578674216 -14.855585162431051},{-35.118606741265054 -33.00455404223835 -13.412784400595367},{-36.30023295955805 -33.172773248311614 -12.789393849695967},{-37.396098399213365 -33.06357624654339 -13.337963765908942},{-36.22401589209895 -33.471269879876516 -11.291788187456293},{-37.463222185329336 -34.30270376192125 -10.919966371788991},{-37.55448205900263 -35.619509969151274 -11.715073313060199},{-38.6538216409946 -36.10401782266501 -11.98880059220686},{-36.37053195093635 -36.183083352673265 -12.081373985999198},{-36.624684431568774 -37.388328417582294 -12.815120434100198} ]		ago2 = [ {-34.26386300135435 -32.998407428317655 -22.075040189835274},{-33.767972005394476 -31.785329790003857 -22.839707283117654},{-32.81949446748223 -32.50861138609696 -21.886975372856973},{-32.35656815162927 -31.686026101800934 -20.646654174074015},{-32.47337487759003 -32.32592942722871 -19.311619371952094},{-31.909159051353825 -31.40751839168098 -18.34923136745037},{-31.95973567715373 -31.923733461475216 -16.925693518764934},{-33.4412224403542 -32.17676717971283 -16.590469850303663},{-34.11221904893955 -30.92900307598431 -16.645299520315255},{-33.57487543154809 -32.45184072304114 -15.2421522231454},{-33.10647751293254 -31.118043986270415 -14.789162538035006},{-34.00192443298045 -30.31933222157224 -15.429295594757907},{-34.295534080630205 -29.039691289330616 -15.569728708156578},{-34.183700632061864 -28.334200342225728 -14.413358177861756},{-35.10323791540406 -28.51359767071855 -16.576623945878502},{-35.32464590971701 -29.22984459328295 -17.73975671816693},{-34.72983387573878 -30.474848641138685 -17.756175154681134},{-34.929828129067715 -31.39106893129418 -18.815716885120633},{-33.88107103855785 -32.55859275560962 -18.863515261255557},{-34.05251987303332 -33.21145171171779 -17.518611740334293},{-33.33748856327233 -34.44616521213911 -17.461631059934426},{-35.52301088127194 -33.4082201330449 -17.146424444664728},{-35.67873675808378 -33.864851905275984 -15.719809964197012},{-35.04350716039007 -32.713035578674216 -14.855585162431051},{-35.118606741265054 -33.00455404223835 -13.412784400595367},{-36.30023295955805 -33.172773248311614 -12.789393849695967},{-37.396098399213365 -33.06357624654339 -13.337963765908942},{-36.22401589209895 -33.471269879876516 -11.291788187456293},{-37.463222185329336 -34.30270376192125 -10.919966371788991},{-37.55448205900263 -35.619509969151274 -11.715073313060199},{-38.6538216409946 -36.10401782266501 -11.98880059220686},{-36.37053195093635 -36.183083352673265 -12.081373985999198},{-36.624684431568774 -37.388328417582294 -12.815120434100198} ]

Karsten Theis: /* About this page */

2021-09-19T14:44:22Z

About this page

←Older revision		Revision as of 14:44, 19 September 2021
Line 7:		Line 7:
	* [[Opioid receptor]]		* [[Opioid receptor]]
	* [[G protein-coupled receptor]]		* [[G protein-coupled receptor]]
		+	* [[Mu Opioid Receptor Bound to a Morphinan Antagonist]]

	== Relevance ==		== Relevance ==

Karsten Theis: /* Structural highlights */

2020-01-07T21:59:52Z

Structural highlights

←Older revision		Revision as of 21:59, 7 January 2020
Line 73:		Line 73:
	In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> set refreshing false; load $oxycodone; background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG"; select _C; color mediumpurple; hide _H; moveto 1.0 { -977 204 68 164.66} 5.0 -34.67 36.52 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0; set zshade on; set zshadepower 1; set spinY 0; set spinX 90; spin on;</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>set refreshing false; load $heroin; background image "http://proteopedia.org/wiki/images/e/e6/OpioidFatality3.JPG"; select _C; color orange; hide _H; set zshade on; set zshadepower 1; moveto 1.0 { 970 216 -113 30.11} 5.0 -8.1 36.32 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { 997 68 23 122.37} 42.42 3.87 -19.17 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>set refreshing false; load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1; background image "http://proteopedia.org/wiki/images/5/51/OpioidFatality4.JPG"; moveto 1.0 { 802 6 -597 24.36} 5.1 32.85 34.38 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0;; set refreshing true; moveto 1.0 { -997 -67 -31 130.64} 55.02 -9.39 -19.75 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>fentanyl</text></jmolLink></jmol>.		In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> set refreshing false; load $oxycodone; background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG"; select _C; color mediumpurple; hide _H; moveto 1.0 { -977 204 68 164.66} 5.0 -34.67 36.52 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0; set zshade on; set zshadepower 1; set spinY 0; set spinX 90; spin on;</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>set refreshing false; load $heroin; background image "http://proteopedia.org/wiki/images/e/e6/OpioidFatality3.JPG"; select _C; color orange; hide _H; set zshade on; set zshadepower 1; moveto 1.0 { 970 216 -113 30.11} 5.0 -8.1 36.32 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { 997 68 23 122.37} 42.42 3.87 -19.17 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>set refreshing false; load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1; background image "http://proteopedia.org/wiki/images/5/51/OpioidFatality4.JPG"; moveto 1.0 { 802 6 -597 24.36} 5.1 32.85 34.38 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0;; set refreshing true; moveto 1.0 { -997 -67 -31 130.64} 55.02 -9.39 -19.75 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>fentanyl</text></jmolLink></jmol>.

-	~~When~~ naloxone ~~is administered to reverse~~ an overdose, ~~it competes with~~ <scene name='83/830406/Competition/1'>the opioid agonist ~~bound to the receptor~~</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]	+	To explore how naloxone reverses an overdose, let's look at the situation during an overdose. The opioid receptor binding pocket is occupied by <scene name='83/830406/Competition/1'>the opioid agonist</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]
	ago1 = [ {-28.15225471470447 -16.732834272032683 -19.877771911210033},{-27.699108229899412 -15.289706379445466 -19.75851945234414},{-26.68480597889424 -16.41202791313621 -19.553508919395476},{-26.088235349655854 -16.524656204830176 -18.11797335653394},{-26.09670821218129 -17.86095364239696 -17.47014979339886},{-25.422698574661922 -17.721641670729095 -16.199593937451922},{-25.353924216489737 -19.013933850033702 -15.411718940408532},{-26.803804141690954 -19.477321003972328 -15.178642669494419},{-27.445395730810528 -18.494213544008844 -14.383647100365163},{-26.818636191572715 -20.537559246853444 -14.291420105179995},{-26.27682344603074 -19.760003263026004 -13.14885472815232},{-27.207435082797755 -18.77153045507903 -13.06873301160048},{-27.480530055558386 -17.69570033702936 -12.353598273980962},{-27.244161412119684 -17.860947196252614 -11.025351181036363},{-28.364696788636234 -16.68825679789819 -12.736096252513157},{-28.711030406563342 -16.531400987159827 -14.066644365033392},{-28.151812675248582 -17.470874662546446 -14.908529596070698},{-28.472248612776976 -17.533960092984973 -16.285274684460944},{-27.462151991406987 -18.37594262285864 -17.143213047564316},{-27.524423894082027 -19.730606208555294 -16.490990861706834},{-26.83847374040866 -20.703170645740975 -17.280056639824984},{-28.958513651925706 -20.17265541019972 -16.19507859468611},{-28.992617235384415 -21.42435546162589 -15.35837319440775},{-28.25116136928705 -21.038824300654305 -14.024697475745336},{-28.19935710109749 -22.168541971976264 -13.079524845534207},{-29.32189117303061 -22.73375369850398 -12.596195804874707},{-30.46083909789644 -22.348636080546093 -12.857454383264495},{-29.114561027297814 -23.897271044635005 -11.626157869573909},{-30.33443496035501 -24.825982830819825 -11.746855863131952},{-30.532177135749723 -25.36260046177555 -13.177744241104742},{-31.66401160803267 -25.612658051750717 -13.595648451478052},{-29.401879118904926 -25.52914420794582 -13.91816207836175},{-29.753259103332216 -26.02310392303815 -15.217442227678971} ]		ago1 = [ {-28.15225471470447 -16.732834272032683 -19.877771911210033},{-27.699108229899412 -15.289706379445466 -19.75851945234414},{-26.68480597889424 -16.41202791313621 -19.553508919395476},{-26.088235349655854 -16.524656204830176 -18.11797335653394},{-26.09670821218129 -17.86095364239696 -17.47014979339886},{-25.422698574661922 -17.721641670729095 -16.199593937451922},{-25.353924216489737 -19.013933850033702 -15.411718940408532},{-26.803804141690954 -19.477321003972328 -15.178642669494419},{-27.445395730810528 -18.494213544008844 -14.383647100365163},{-26.818636191572715 -20.537559246853444 -14.291420105179995},{-26.27682344603074 -19.760003263026004 -13.14885472815232},{-27.207435082797755 -18.77153045507903 -13.06873301160048},{-27.480530055558386 -17.69570033702936 -12.353598273980962},{-27.244161412119684 -17.860947196252614 -11.025351181036363},{-28.364696788636234 -16.68825679789819 -12.736096252513157},{-28.711030406563342 -16.531400987159827 -14.066644365033392},{-28.151812675248582 -17.470874662546446 -14.908529596070698},{-28.472248612776976 -17.533960092984973 -16.285274684460944},{-27.462151991406987 -18.37594262285864 -17.143213047564316},{-27.524423894082027 -19.730606208555294 -16.490990861706834},{-26.83847374040866 -20.703170645740975 -17.280056639824984},{-28.958513651925706 -20.17265541019972 -16.19507859468611},{-28.992617235384415 -21.42435546162589 -15.35837319440775},{-28.25116136928705 -21.038824300654305 -14.024697475745336},{-28.19935710109749 -22.168541971976264 -13.079524845534207},{-29.32189117303061 -22.73375369850398 -12.596195804874707},{-30.46083909789644 -22.348636080546093 -12.857454383264495},{-29.114561027297814 -23.897271044635005 -11.626157869573909},{-30.33443496035501 -24.825982830819825 -11.746855863131952},{-30.532177135749723 -25.36260046177555 -13.177744241104742},{-31.66401160803267 -25.612658051750717 -13.595648451478052},{-29.401879118904926 -25.52914420794582 -13.91816207836175},{-29.753259103332216 -26.02310392303815 -15.217442227678971} ]
	ago2 = [ {-34.26386300135435 -32.998407428317655 -22.075040189835274},{-33.767972005394476 -31.785329790003857 -22.839707283117654},{-32.81949446748223 -32.50861138609696 -21.886975372856973},{-32.35656815162927 -31.686026101800934 -20.646654174074015},{-32.47337487759003 -32.32592942722871 -19.311619371952094},{-31.909159051353825 -31.40751839168098 -18.34923136745037},{-31.95973567715373 -31.923733461475216 -16.925693518764934},{-33.4412224403542 -32.17676717971283 -16.590469850303663},{-34.11221904893955 -30.92900307598431 -16.645299520315255},{-33.57487543154809 -32.45184072304114 -15.2421522231454},{-33.10647751293254 -31.118043986270415 -14.789162538035006},{-34.00192443298045 -30.31933222157224 -15.429295594757907},{-34.295534080630205 -29.039691289330616 -15.569728708156578},{-34.183700632061864 -28.334200342225728 -14.413358177861756},{-35.10323791540406 -28.51359767071855 -16.576623945878502},{-35.32464590971701 -29.22984459328295 -17.73975671816693},{-34.72983387573878 -30.474848641138685 -17.756175154681134},{-34.929828129067715 -31.39106893129418 -18.815716885120633},{-33.88107103855785 -32.55859275560962 -18.863515261255557},{-34.05251987303332 -33.21145171171779 -17.518611740334293},{-33.33748856327233 -34.44616521213911 -17.461631059934426},{-35.52301088127194 -33.4082201330449 -17.146424444664728},{-35.67873675808378 -33.864851905275984 -15.719809964197012},{-35.04350716039007 -32.713035578674216 -14.855585162431051},{-35.118606741265054 -33.00455404223835 -13.412784400595367},{-36.30023295955805 -33.172773248311614 -12.789393849695967},{-37.396098399213365 -33.06357624654339 -13.337963765908942},{-36.22401589209895 -33.471269879876516 -11.291788187456293},{-37.463222185329336 -34.30270376192125 -10.919966371788991},{-37.55448205900263 -35.619509969151274 -11.715073313060199},{-38.6538216409946 -36.10401782266501 -11.98880059220686},{-36.37053195093635 -36.183083352673265 -12.081373985999198},{-36.624684431568774 -37.388328417582294 -12.815120434100198} ]		ago2 = [ {-34.26386300135435 -32.998407428317655 -22.075040189835274},{-33.767972005394476 -31.785329790003857 -22.839707283117654},{-32.81949446748223 -32.50861138609696 -21.886975372856973},{-32.35656815162927 -31.686026101800934 -20.646654174074015},{-32.47337487759003 -32.32592942722871 -19.311619371952094},{-31.909159051353825 -31.40751839168098 -18.34923136745037},{-31.95973567715373 -31.923733461475216 -16.925693518764934},{-33.4412224403542 -32.17676717971283 -16.590469850303663},{-34.11221904893955 -30.92900307598431 -16.645299520315255},{-33.57487543154809 -32.45184072304114 -15.2421522231454},{-33.10647751293254 -31.118043986270415 -14.789162538035006},{-34.00192443298045 -30.31933222157224 -15.429295594757907},{-34.295534080630205 -29.039691289330616 -15.569728708156578},{-34.183700632061864 -28.334200342225728 -14.413358177861756},{-35.10323791540406 -28.51359767071855 -16.576623945878502},{-35.32464590971701 -29.22984459328295 -17.73975671816693},{-34.72983387573878 -30.474848641138685 -17.756175154681134},{-34.929828129067715 -31.39106893129418 -18.815716885120633},{-33.88107103855785 -32.55859275560962 -18.863515261255557},{-34.05251987303332 -33.21145171171779 -17.518611740334293},{-33.33748856327233 -34.44616521213911 -17.461631059934426},{-35.52301088127194 -33.4082201330449 -17.146424444664728},{-35.67873675808378 -33.864851905275984 -15.719809964197012},{-35.04350716039007 -32.713035578674216 -14.855585162431051},{-35.118606741265054 -33.00455404223835 -13.412784400595367},{-36.30023295955805 -33.172773248311614 -12.789393849695967},{-37.396098399213365 -33.06357624654339 -13.337963765908942},{-36.22401589209895 -33.471269879876516 -11.291788187456293},{-37.463222185329336 -34.30270376192125 -10.919966371788991},{-37.55448205900263 -35.619509969151274 -11.715073313060199},{-38.6538216409946 -36.10401782266501 -11.98880059220686},{-36.37053195093635 -36.183083352673265 -12.081373985999198},{-36.624684431568774 -37.388328417582294 -12.815120434100198} ]

Karsten Theis: /* Structural highlights */

2020-01-07T21:54:07Z

Structural highlights

←Older revision		Revision as of 21:54, 7 January 2020
Line 71:		Line 71:
	Try rotating the molecule after turning off the automatic spinning (+/- spin button). Zooming in on the <scene name='83/830406/Peptide/2'>signalling molecule</scene>, you see it is deeply buried within the protein. Binding results in a change of shape of the receptor (not shown here) to relay the signal to the inside of the cell.		Try rotating the molecule after turning off the automatic spinning (+/- spin button). Zooming in on the <scene name='83/830406/Peptide/2'>signalling molecule</scene>, you see it is deeply buried within the protein. Binding results in a change of shape of the receptor (not shown here) to relay the signal to the inside of the cell.

-	In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> set refreshing false; load $oxycodone; background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG"; select _C; color mediumpurple; hide _H; moveto 1.0 { -977 204 68 164.66} 5.0 -34.67 36.52 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0; set zshade on; set zshadepower 1</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>set refreshing false; load $heroin; background image "http://proteopedia.org/wiki/images/e/e6/OpioidFatality3.JPG"; select _C; color orange; hide _H; set zshade on; set zshadepower 1; moveto 1.0 { 970 216 -113 30.11} 5.0 -8.1 36.32 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { 997 68 23 122.37} 42.42 3.87 -19.17 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; </script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>set refreshing false; load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1; background image "http://proteopedia.org/wiki/images/5/51/OpioidFatality4.JPG"; moveto 1.0 { 802 6 -597 24.36} 5.1 32.85 34.38 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0;; set refreshing true; moveto 1.0 { -997 -67 -31 130.64} 55.02 -9.39 -19.75 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0;</script><text>fentanyl</text></jmolLink></jmol>.	+	In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> set refreshing false; load $oxycodone; background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG"; select _C; color mediumpurple; hide _H; moveto 1.0 { -977 204 68 164.66} 5.0 -34.67 36.52 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0; set zshade on; set zshadepower 1; set spinY 0; set spinX 90; spin on;</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>set refreshing false; load $heroin; background image "http://proteopedia.org/wiki/images/e/e6/OpioidFatality3.JPG"; select _C; color orange; hide _H; set zshade on; set zshadepower 1; moveto 1.0 { 970 216 -113 30.11} 5.0 -8.1 36.32 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { 997 68 23 122.37} 42.42 3.87 -19.17 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>set refreshing false; load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1; background image "http://proteopedia.org/wiki/images/5/51/OpioidFatality4.JPG"; moveto 1.0 { 802 6 -597 24.36} 5.1 32.85 34.38 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0;; set refreshing true; moveto 1.0 { -997 -67 -31 130.64} 55.02 -9.39 -19.75 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>fentanyl</text></jmolLink></jmol>.

	When naloxone is administered to reverse an overdose, it competes with <scene name='83/830406/Competition/1'>the opioid agonist bound to the receptor</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]		When naloxone is administered to reverse an overdose, it competes with <scene name='83/830406/Competition/1'>the opioid agonist bound to the receptor</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]

Karsten Theis: /* Structural highlights */

2020-01-07T21:45:52Z

Structural highlights

←Older revision		Revision as of 21:45, 7 January 2020
Line 71:		Line 71:
	Try rotating the molecule after turning off the automatic spinning (+/- spin button). Zooming in on the <scene name='83/830406/Peptide/2'>signalling molecule</scene>, you see it is deeply buried within the protein. Binding results in a change of shape of the receptor (not shown here) to relay the signal to the inside of the cell.		Try rotating the molecule after turning off the automatic spinning (+/- spin button). Zooming in on the <scene name='83/830406/Peptide/2'>signalling molecule</scene>, you see it is deeply buried within the protein. Binding results in a change of shape of the receptor (not shown here) to relay the signal to the inside of the cell.

-	In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> load $oxycodone; background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG"; select _C; color mediumpurple; hide _H; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0; set zshade on; set zshadepower 1</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>set refreshing false; load $heroin; background ~~white~~; select _C; color orange; hide _H; set zshade on; set zshadepower 1; moveto 1.0 { 970 216 -113 30.11} 5.0 -8.1 36.32 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { 997 68 23 122.37} 42.42 3.87 -19.17 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; </script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1</script><text>fentanyl</text></jmolLink></jmol>.	+	In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> set refreshing false; load $oxycodone; background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG"; select _C; color mediumpurple; hide _H; moveto 1.0 { -977 204 68 164.66} 5.0 -34.67 36.52 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0; set zshade on; set zshadepower 1</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>set refreshing false; load $heroin; background image "http://proteopedia.org/wiki/images/e/e6/OpioidFatality3.JPG"; select _C; color orange; hide _H; set zshade on; set zshadepower 1; moveto 1.0 { 970 216 -113 30.11} 5.0 -8.1 36.32 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { 997 68 23 122.37} 42.42 3.87 -19.17 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; </script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>set refreshing false; load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1; background image "http://proteopedia.org/wiki/images/5/51/OpioidFatality4.JPG"; moveto 1.0 { 802 6 -597 24.36} 5.1 32.85 34.38 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0;; set refreshing true; moveto 1.0 { -997 -67 -31 130.64} 55.02 -9.39 -19.75 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0;</script><text>fentanyl</text></jmolLink></jmol>.

	When naloxone is administered to reverse an overdose, it competes with <scene name='83/830406/Competition/1'>the opioid agonist bound to the receptor</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]		When naloxone is administered to reverse an overdose, it competes with <scene name='83/830406/Competition/1'>the opioid agonist bound to the receptor</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]

Karsten Theis: /* Structural highlights */

2020-01-07T21:38:06Z

Structural highlights

←Older revision		Revision as of 21:38, 7 January 2020
Line 71:		Line 71:
	Try rotating the molecule after turning off the automatic spinning (+/- spin button). Zooming in on the <scene name='83/830406/Peptide/2'>signalling molecule</scene>, you see it is deeply buried within the protein. Binding results in a change of shape of the receptor (not shown here) to relay the signal to the inside of the cell.		Try rotating the molecule after turning off the automatic spinning (+/- spin button). Zooming in on the <scene name='83/830406/Peptide/2'>signalling molecule</scene>, you see it is deeply buried within the protein. Binding results in a change of shape of the receptor (not shown here) to relay the signal to the inside of the cell.

-	In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> load $oxycodone; select _C; color mediumpurple; hide _H; set zshade on; set zshadepower 1</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>load $heroin; background white; select _C; color orange; hide _H; set zshade on; set zshadepower 1</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1</script><text>fentanyl</text></jmolLink></jmol>.	+	In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> load $oxycodone; background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG"; select _C; color mediumpurple; hide _H; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0; set zshade on; set zshadepower 1</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>set refreshing false; load $heroin; background white; select _C; color orange; hide _H; set zshade on; set zshadepower 1; moveto 1.0 { 970 216 -113 30.11} 5.0 -8.1 36.32 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { 997 68 23 122.37} 42.42 3.87 -19.17 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; </script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1</script><text>fentanyl</text></jmolLink></jmol>.

	When naloxone is administered to reverse an overdose, it competes with <scene name='83/830406/Competition/1'>the opioid agonist bound to the receptor</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]		When naloxone is administered to reverse an overdose, it competes with <scene name='83/830406/Competition/1'>the opioid agonist bound to the receptor</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]

Karsten Theis: /* Structural highlights */

2020-01-07T21:27:42Z

Structural highlights

←Older revision		Revision as of 21:27, 7 January 2020
Line 71:		Line 71:
	Try rotating the molecule after turning off the automatic spinning (+/- spin button). Zooming in on the <scene name='83/830406/Peptide/2'>signalling molecule</scene>, you see it is deeply buried within the protein. Binding results in a change of shape of the receptor (not shown here) to relay the signal to the inside of the cell.		Try rotating the molecule after turning off the automatic spinning (+/- spin button). Zooming in on the <scene name='83/830406/Peptide/2'>signalling molecule</scene>, you see it is deeply buried within the protein. Binding results in a change of shape of the receptor (not shown here) to relay the signal to the inside of the cell.

-	In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> load $oxycodone; select _C; color mediumpurple; hide _H; set zshade on; set zshadepower 1</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>load $heroin; background white; select _C; color orange; hide _H; set zshade on; set zshadepower 1</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>~~background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality4.JPG";~~ load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1</script><text>fentanyl</text></jmolLink></jmol>.	+	In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> load $oxycodone; select _C; color mediumpurple; hide _H; set zshade on; set zshadepower 1</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>load $heroin; background white; select _C; color orange; hide _H; set zshade on; set zshadepower 1</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1</script><text>fentanyl</text></jmolLink></jmol>.

	When naloxone is administered to reverse an overdose, it competes with <scene name='83/830406/Competition/1'>the opioid agonist bound to the receptor</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]		When naloxone is administered to reverse an overdose, it competes with <scene name='83/830406/Competition/1'>the opioid agonist bound to the receptor</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]

Karsten Theis: /* Structural highlights */

2020-01-07T21:24:28Z

Structural highlights

←Older revision		Revision as of 21:24, 7 January 2020
Line 71:		Line 71:
	Try rotating the molecule after turning off the automatic spinning (+/- spin button). Zooming in on the <scene name='83/830406/Peptide/2'>signalling molecule</scene>, you see it is deeply buried within the protein. Binding results in a change of shape of the receptor (not shown here) to relay the signal to the inside of the cell.		Try rotating the molecule after turning off the automatic spinning (+/- spin button). Zooming in on the <scene name='83/830406/Peptide/2'>signalling molecule</scene>, you see it is deeply buried within the protein. Binding results in a change of shape of the receptor (not shown here) to relay the signal to the inside of the cell.

-	In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> ~~background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG";~~ load $oxycodone; select _C; color mediumpurple; hide _H~~; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0~~; set zshade on; set zshadepower 1</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>load $heroin; select _C; color orange; hide _H; set zshade on; set zshadepower 1</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality4.JPG"; load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1</script><text>fentanyl</text></jmolLink></jmol>.	+	In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> load $oxycodone; select _C; color mediumpurple; hide _H; set zshade on; set zshadepower 1</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>load $heroin; background white; select _C; color orange; hide _H; set zshade on; set zshadepower 1</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality4.JPG"; load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1</script><text>fentanyl</text></jmolLink></jmol>.

	When naloxone is administered to reverse an overdose, it competes with <scene name='83/830406/Competition/1'>the opioid agonist bound to the receptor</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]		When naloxone is administered to reverse an overdose, it competes with <scene name='83/830406/Competition/1'>the opioid agonist bound to the receptor</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]

Karsten Theis: /* Natural Function */

2020-01-07T21:10:05Z

Natural Function

←Older revision		Revision as of 21:10, 7 January 2020
Line 21:		Line 21:
	The part of the receptor that interacts with the G proteins can also bind to another protein in the cell called [[arrestin]]. Arrestin, as its name suggest, stops a given receptor from always being on. When arrestin is bound, the receptor and a bit of the membrane it is integrated in form a tiny cell-like structure called a vesicle with the opioid binding site pointing inside (see figure at right). Due to increased acidity in the vesicle, the opioid receptor releases the bound opioid. Then, one of two events may occur; either the receptor is delivered back to the cell membrane, or it is broken down into its building blocks.		The part of the receptor that interacts with the G proteins can also bind to another protein in the cell called [[arrestin]]. Arrestin, as its name suggest, stops a given receptor from always being on. When arrestin is bound, the receptor and a bit of the membrane it is integrated in form a tiny cell-like structure called a vesicle with the opioid binding site pointing inside (see figure at right). Due to increased acidity in the vesicle, the opioid receptor releases the bound opioid. Then, one of two events may occur; either the receptor is delivered back to the cell membrane, or it is broken down into its building blocks.

-	To see the receptor in action, you can watch a 4:35 min. video [https://www.youtube.com/watch?v=8BcINeVoOWQ (video <span class="fas fa-video" style="color:#338fff"></span>)] that connects the activity of an individual with the switching of the receptor in the cell	+	To see the physical model of the receptor in action, you can watch a 4:35 min. video [https://www.youtube.com/watch?v=8BcINeVoOWQ (video <span class="fas fa-video" style="color:#338fff"></span>)] that connects the activity of a human individual with the switching of the receptor in the cell.

	== Tolerance and Abuse==		== Tolerance and Abuse==

Karsten Theis at 02:24, 28 December 2019

2019-12-28T02:24:00Z

←Older revision		Revision as of 02:24, 28 December 2019
Line 1:		Line 1:
-	[[Image:Receptor.gif\|frame\|200\|Conceptual model of the opioid receptor. Parts of the receptor between the two cardboard pieces are integrated in the cell membrane, with other parts sticking out and ~~"sticking in"~~]]	+	[[Image:Receptor.gif\|frame\|200\|Conceptual model of the opioid receptor. Parts of the receptor between the two cardboard pieces are integrated in the cell membrane, with other parts sticking out and reaching into the cell]]
	The '''opioid receptor''', a protein on the surface of nerve cells, binds to opioids such as morphine, oxicodone, heroin, and fentanyl, leading to the inability to feel pain. Repeated intake of opioids changes the response to these molecules, and can lead to addiction.		The '''opioid receptor''', a protein on the surface of nerve cells, binds to opioids such as morphine, oxicodone, heroin, and fentanyl, leading to the inability to feel pain. Repeated intake of opioids changes the response to these molecules, and can lead to addiction.