7rq8 - Revision history

OCA at 11:10, 15 November 2023

2023-11-15T11:10:33Z

←Older revision		Revision as of 11:10, 15 November 2023
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	==See Also==		==See Also==
		+	*[[Ribosomal protein THX 3D structures\|Ribosomal protein THX 3D structures]]
	*[[Ribosome 3D structures\|Ribosome 3D structures]]		*[[Ribosome 3D structures\|Ribosome 3D structures]]
	== References ==		== References ==

OCA at 16:36, 18 October 2023

2023-10-18T16:36:05Z

←Older revision		Revision as of 16:36, 18 October 2023
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-	====	+	==Crystal structure of the wild-type Thermus thermophilus 70S ribosome in complex with iboxamycin, mRNA, deacylated A- and E-site tRNAs, and aminoacylated P-site tRNA at 2.50A resolution==
-	<StructureSection load='7rq8' size='340' side='right'caption='[[7rq8]]' scene=''>	+	<StructureSection load='7rq8' size='340' side='right'caption='[[7rq8]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7rq8]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB8 Thermus thermophilus HB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RQ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RQ8 FirstGlance]. <br>
-	</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=7rq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rq8 OCA], [https://pdbe.org/7rq8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rq8 RCSB], [https://www.ebi.ac.uk/pdbsum/7rq8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rq8 ProSAT]</span></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]] 2.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0TD:(3S)-3-(METHYLSULFANYL)-L-ASPARTIC+ACID'>0TD</scene>, <scene name='pdbligand=2MA:2-METHYLADENOSINE-5-MONOPHOSPHATE'>2MA</scene>, <scene name='pdbligand=2MG:2N-METHYLGUANOSINE-5-MONOPHOSPHATE'>2MG</scene>, <scene name='pdbligand=31H:3-DEOXY-3-[(N-FORMYL-L-METHIONYL)AMINO]ADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>31H</scene>, <scene name='pdbligand=4OC:4N,O2-METHYLCYTIDINE-5-MONOPHOSPHATE'>4OC</scene>, <scene name='pdbligand=4SU:4-THIOURIDINE-5-MONOPHOSPHATE'>4SU</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</scene>, <scene name='pdbligand=5MU:5-METHYLURIDINE+5-MONOPHOSPHATE'>5MU</scene>, <scene name='pdbligand=6IF:methyl+7-chloro-6,7,8-trideoxy-6-{[(4S,5aS,8S,8aR)-4-(2-methylpropyl)octahydro-2H-oxepino[2,3-c]pyrrole-8-carbonyl]amino}-1-thio-L-threo-alpha-D-galacto-octopyranoside'>6IF</scene>, <scene name='pdbligand=7MG:7N-METHYL-8-HYDROGUANOSINE-5-MONOPHOSPHATE'>7MG</scene>, <scene name='pdbligand=F3N:3-DEOXY-3-(L-PHENYLALANYLAMINO)ADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>F3N</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=M2G:N2-DIMETHYLGUANOSINE-5-MONOPHOSPHATE'>M2G</scene>, <scene name='pdbligand=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MIA:2-METHYLTHIO-N6-ISOPENTENYL-ADENOSINE-5-MONOPHOSPHATE'>MIA</scene>, <scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=OMU:O2-METHYLURIDINE+5-MONOPHOSPHATE'>OMU</scene>, <scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=UR3:3-METHYLURIDINE-5-MONOPHOSHATE'>UR3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=7rq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rq8 OCA], [https://pdbe.org/7rq8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rq8 RCSB], [https://www.ebi.ac.uk/pdbsum/7rq8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rq8 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/RL2_THET8 RL2_THET8] One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial (By similarity). Makes several contacts with the 16S rRNA (forming bridge B7b) in the 70S ribosome.[HAMAP-Rule:MF_01320_B]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The dearth of new medicines effective against antibiotic-resistant bacteria presents a growing global public health concern(1). For more than five decades, the search for new antibiotics has relied heavily on the chemical modification of natural products (semisynthesis), a method ill-equipped to combat rapidly evolving resistance threats. Semisynthetic modifications are typically of limited scope within polyfunctional antibiotics, usually increase molecular weight, and seldom permit modifications of the underlying scaffold. When properly designed, fully synthetic routes can easily address these shortcomings(2). Here we report the structure-guided design and component-based synthesis of a rigid oxepanoproline scaffold which, when linked to the aminooctose residue of clindamycin, produces an antibiotic of exceptional potency and spectrum of activity, which we name iboxamycin. Iboxamycin is effective against ESKAPE pathogens including strains expressing Erm and Cfr ribosomal RNA methyltransferase enzymes, products of genes that confer resistance to all clinically relevant antibiotics targeting the large ribosomal subunit, namely macrolides, lincosamides, phenicols, oxazolidinones, pleuromutilins and streptogramins. X-ray crystallographic studies of iboxamycin in complex with the native bacterial ribosome, as well as with the Erm-methylated ribosome, uncover the structural basis for this enhanced activity, including a displacement of the [Formula: see text] nucleotide upon antibiotic binding. Iboxamycin is orally bioavailable, safe and effective in treating both Gram-positive and Gram-negative bacterial infections in mice, attesting to the capacity for chemical synthesis to provide new antibiotics in an era of increasing resistance.
		+
		+	A synthetic antibiotic class overcoming bacterial multidrug resistance.,Mitcheltree MJ, Pisipati A, Syroegin EA, Silvestre KJ, Klepacki D, Mason JD, Terwilliger DW, Testolin G, Pote AR, Wu KJY, Ladley RP, Chatman K, Mankin AS, Polikanov YS, Myers AG Nature. 2021 Nov;599(7885):507-512. doi: 10.1038/s41586-021-04045-6. Epub 2021 , Oct 27. PMID:34707295<ref>PMID:34707295</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7rq8" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ribosome 3D structures\|Ribosome 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Thermus thermophilus HB8]]
		+	[[Category: Chatman K]]
		+	[[Category: Klepacki D]]
		+	[[Category: Ladley RP]]
		+	[[Category: Mankin AS]]
		+	[[Category: Mason JD]]
		+	[[Category: Mitcheltree MJ]]
		+	[[Category: Myers AG]]
		+	[[Category: Pisipati A]]
		+	[[Category: Polikanov YS]]
		+	[[Category: Pote AR]]
		+	[[Category: Silvestre KJ]]
		+	[[Category: Syroegin EA]]
		+	[[Category: Terwilliger DW]]
		+	[[Category: Testolin G]]
		+	[[Category: Wu KJY]]

OCA at 11:46, 13 October 2021

2021-10-13T11:46:45Z

←Older revision		Revision as of 11:46, 13 October 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7rq8 ~~is ON HOLD~~	+	====
-		+	<StructureSection load='7rq8' size='340' side='right'caption='[[7rq8]]' scene=''>
-	~~Authors~~: ~~Mitcheltree, M~~.J.~~, Pisipati, A~~.~~, Syroegin, E~~.~~A., Silvestre, K.J., Klepacki, D., Mason, J.D., Terwilliger, D.W., Testolin, G., Pote, A.R., Wu, K.J.Y., Ladley, R.P., Chatman, K., Mankin, A.S., Polikanov, Y.S., Myers, A.G.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description: Crystal~~ structure ~~of the wild-type Thermus thermophilus 70S ribosome in complex with iboxamycin, mRNA, deacylated A-and E-site tRNAs, and aminoacylated P-site tRNA at 2.50A resolution~~	+	</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=7rq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rq8 OCA], [https://pdbe.org/7rq8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rq8 RCSB], [https://www.ebi.ac.uk/pdbsum/7rq8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rq8 ProSAT]</span></td></tr>
-	[~~[Category~~: ~~Unreleased Structures~~]]	+	</table>
-	~~[[Category: Mankin, A~~.~~S]]~~	+	__TOC__
-	~~[[Category~~: ~~Chatman, K]]~~	+	</StructureSection>
-	[~~[Category~~: ~~Ladley, R~~.P]]	+	[[Category: Large Structures]]
-	~~[[Category: Pote~~, ~~A.R]]~~	+	[[Category: Z-disk]]
-	[~~[Category~~: ~~Polikanov, Y~~.S]]	+
-	~~[[Category: Testolin~~, ~~G]]~~	+
-	[~~[Category~~: ~~Syroegin, E~~.A]]	+
-	[~~[Category~~: ~~Mitcheltree, M~~.J]]	+
-	~~[[Category: Pisipati~~, ~~A]]~~	+
-	[~~[Category~~: ~~Klepacki, D]]~~	+
-	~~[[Category: Silvestre, K~~.~~J]]~~	+
-	~~[[Category: Wu, K~~.J.Y]]	+
-	[~~[Category~~: ~~Terwilliger, D~~.W]]	+
-	[[Category: ~~Myers, A.G~~]]	+
-	[[Category: ~~Mason, J.D~~]]	+

OCA: Protected "7rq8" [edit=sysop:move=sysop]

2021-08-11T05:13:53Z

Protected "7rq8" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:13, 11 August 2021

OCA: New page: '''Unreleased structure''' The entry 7rq8 is ON HOLD Authors: Mitcheltree, M.J., Pisipati, A., Syroegin, E.A., Silvestre, K.J., Klepacki, D., Mason, J.D., Terwilliger, D.W., Testolin, G...

2021-08-11T05:13:52Z

New page: '''Unreleased structure''' The entry 7rq8 is ON HOLD Authors: Mitcheltree, M.J., Pisipati, A., Syroegin, E.A., Silvestre, K.J., Klepacki, D., Mason, J.D., Terwilliger, D.W., Testolin, G...

New page

'''Unreleased structure'''

The entry 7rq8 is ON HOLD

Authors: Mitcheltree, M.J., Pisipati, A., Syroegin, E.A., Silvestre, K.J., Klepacki, D., Mason, J.D., Terwilliger, D.W., Testolin, G., Pote, A.R., Wu, K.J.Y., Ladley, R.P., Chatman, K., Mankin, A.S., Polikanov, Y.S., Myers, A.G.

Description: Crystal structure of the wild-type Thermus thermophilus 70S ribosome in complex with iboxamycin, mRNA, deacylated A-and E-site tRNAs, and aminoacylated P-site tRNA at 2.50A resolution
[[Category: Unreleased Structures]]
[[Category: Mankin, A.S]]
[[Category: Chatman, K]]
[[Category: Ladley, R.P]]
[[Category: Pote, A.R]]
[[Category: Polikanov, Y.S]]
[[Category: Testolin, G]]
[[Category: Syroegin, E.A]]
[[Category: Mitcheltree, M.J]]
[[Category: Pisipati, A]]
[[Category: Klepacki, D]]
[[Category: Silvestre, K.J]]
[[Category: Wu, K.J.Y]]
[[Category: Terwilliger, D.W]]
[[Category: Myers, A.G]]
[[Category: Mason, J.D]]