This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3uas

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Cytochrome P450 2B4 covalently bound to the mechanism-based inactivator 9-ethynylphenanthrene

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3uas"

@@ Line 3: / Line 3: @@
 <StructureSection load='3uas' size='340' side='right'caption='[[3uas]], [[Resolution|resolution]] 2.94&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3uas]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UAS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UAS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3uas]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UAS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UAS FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0BV:PHENANTHREN-9-YLACETALDEHYDE'>0BV</scene>, <scene name='pdbligand=CM5:5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE'>CM5</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.939&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2B4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0BV:PHENANTHREN-9-YLACETALDEHYDE'>0BV</scene>, <scene name='pdbligand=CM5:5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE'>CM5</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3uas FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uas OCA], [https://pdbe.org/3uas PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uas RCSB], [https://www.ebi.ac.uk/pdbsum/3uas PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uas ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT]] Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.
+[https://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT] Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-The mechanism-based inactivation of cytochrome P450 2B4 (CYP2B4) by 9-ethynylphenanthrene (9EP) has been investigated. The partition ratio and k(inact) are 0.2 and 0.25 min(-1), respectively. Intriguingly, the inactivation exhibits sigmoidal kinetics with a Hill coefficient of 2.5 and an S(50) of 4.5 muM indicative of homotropic cooperativity. Enzyme inactivation led to an increase in mass of the apo-CYP2B4 by 218 Da as determined by electrospray ionization liquid chromatography and mass spectrometry, consistent with covalent protein modification. The modified CYP2B4 was purified to homogeneity and its structure determined by X-ray crystallography. The structure showed that 9EP is covalently attached to Ogamma of Thr 302 via an ester bond, which is consistent with the increased mass of the protein. The presence of the bulky phenanthrenyl ring resulted in inward rotations of Phe 297 and Phe 206, leading to a compact active site. Thus, binding of another molecule of 9EP in the active site is prohibited. However, results from the quenching of 9EP fluorescence by unmodified or 9EP-modified CYP2B4 revealed at least two binding sites with distinct affinities, with the low-affinity site being the catalytic site and the high-affinity site on the protein periphery. Computer-aided docking and molecular dynamics simulations with one or two ligands bound revealed that the high-affinity site is situated at the entrance of a substrate access channel surrounded by the F' helix, beta1-beta2 loop, and beta4 loop and functions as an allosteric site to enhance the efficiency of activation of the acetylenic group of 9EP and subsequent covalent modification of Thr 302.
-Potent Mechanism-Based Inactivation of Cytochrome P450 2B4 by 9-Ethynylphenanthrene: Implications for Allosteric Modulation of Cytochrome P450 Catalysis.,Zhang H, Gay SC, Shah M, Foroozesh M, Liu J, Osawa Y, Zhang Q, Stout CD, Halpert JR, Hollenberg PF Biochemistry. 2013 Jan 4. PMID:23276288<ref>PMID:23276288</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 3uas" style="background-color:#fffaf0;"></div>
 ==See Also==
 *[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: European rabbit]]
 [[Category: Large Structures]]
-[[Category: Unspecific monooxygenase]]
+[[Category: Oryctolagus cuniculus]]
-[[Category: Gay, S C]]
+[[Category: Gay SC]]
-[[Category: Halpert, J R]]
+[[Category: Halpert JR]]
-[[Category: Hollenberg, P F]]
+[[Category: Hollenberg PF]]
-[[Category: Shah, M B]]
+[[Category: Shah MB]]
-[[Category: Stout, C D]]
+[[Category: Stout CD]]
-[[Category: Zhang, H]]
+[[Category: Zhang H]]
-[[Category: Cyp 2b4]]
-[[Category: Cyp lm2]]
-[[Category: Cytochrome p450 2b4]]
-[[Category: Membrane protein]]
-[[Category: Monooxygenase]]
-[[Category: Oxidoreductase]]
-[[Category: P450]]

3uas

From Proteopedia

Current revision

Cytochrome P450 2B4 covalently bound to the mechanism-based inactivator 9-ethynylphenanthrene

Structural highlights

Function

See Also

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox