6pcs - Revision history

OCA at 06:32, 7 October 2020

OCA — Wed, 07 Oct 2020 06:32:26 GMT

←Older revision		Revision as of 06:32, 7 October 2020
Line 10:		Line 10:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/RL3_ECOLI RL3_ECOLI]] One of two assembly inititator proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit.[HAMAP-Rule:MF_01325_B] [[http://www.uniprot.org/uniprot/A0A037Y8L6_ECOLX A0A037Y8L6_ECOLX]] Binds to the 23S rRNA.[HAMAP-Rule:MF_01341][SAAS:SAAS00124822] [[http://www.uniprot.org/uniprot/RL2_ECOLI RL2_ECOLI]] One of the primary rRNA binding proteins. Located near the base of the L1 stalk, it is probably also mobile. 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 highly controversial.[HAMAP-Rule:MF_01320_B] In the E.coli 70S ribosome in the initiation state it has been modeled to make several contacts with the 16S rRNA (forming bridge B7b, PubMed:12809609); these contacts are broken in the model with bound EF-G.[HAMAP-Rule:MF_01320_B] [[http://www.uniprot.org/uniprot/D7ZET0_ECOLX D7ZET0_ECOLX]] This protein is one of the early assembly proteins of the 50S ribosomal subunit, although it is not seen to bind rRNA by itself. It is important during the early stages of 50S assembly.[HAMAP-Rule:MF_01366][RuleBase:RU003878][SAAS:SAAS00672061] [[http://www.uniprot.org/uniprot/D7Z9F6_ECOLX D7Z9F6_ECOLX]] Forms part of the polypeptide exit tunnel.[HAMAP-Rule:MF_01328] One of the primary rRNA binding proteins, this protein initially binds near the 5'-end of the 23S rRNA. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome.[HAMAP-Rule:MF_01328]		[[http://www.uniprot.org/uniprot/RL3_ECOLI RL3_ECOLI]] One of two assembly inititator proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit.[HAMAP-Rule:MF_01325_B] [[http://www.uniprot.org/uniprot/A0A037Y8L6_ECOLX A0A037Y8L6_ECOLX]] Binds to the 23S rRNA.[HAMAP-Rule:MF_01341][SAAS:SAAS00124822] [[http://www.uniprot.org/uniprot/RL2_ECOLI RL2_ECOLI]] One of the primary rRNA binding proteins. Located near the base of the L1 stalk, it is probably also mobile. 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 highly controversial.[HAMAP-Rule:MF_01320_B] In the E.coli 70S ribosome in the initiation state it has been modeled to make several contacts with the 16S rRNA (forming bridge B7b, PubMed:12809609); these contacts are broken in the model with bound EF-G.[HAMAP-Rule:MF_01320_B] [[http://www.uniprot.org/uniprot/D7ZET0_ECOLX D7ZET0_ECOLX]] This protein is one of the early assembly proteins of the 50S ribosomal subunit, although it is not seen to bind rRNA by itself. It is important during the early stages of 50S assembly.[HAMAP-Rule:MF_01366][RuleBase:RU003878][SAAS:SAAS00672061] [[http://www.uniprot.org/uniprot/D7Z9F6_ECOLX D7Z9F6_ECOLX]] Forms part of the polypeptide exit tunnel.[HAMAP-Rule:MF_01328] One of the primary rRNA binding proteins, this protein initially binds near the 5'-end of the 23S rRNA. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome.[HAMAP-Rule:MF_01328]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Natural products serve as chemical blueprints for most antibiotics in clinical use. The evolutionary process by which these molecules arise is inherently accompanied by the co-evolution of resistance mechanisms that shorten the clinical lifetime of any given class of antibiotics(1). Virginiamycin acetyltransferase (Vat) enzymes are resistance proteins that provide protection against streptogramins(2), potent antibiotics against Gram-positive bacteria that inhibit the bacterial ribosome(3). Owing to the challenge of selectively modifying the chemically complex, 23-membered macrocyclic scaffold of group A streptogramins, analogues that overcome the resistance conferred by Vat enzymes have not been previously developed(2). Here we report the design, synthesis, and antibacterial evaluation of group A streptogramin antibiotics with extensive structural variability. Using cryo-electron microscopy and forcefield-based refinement, we characterize the binding of eight analogues to the bacterial ribosome at high resolution, revealing binding interactions that extend into the peptidyl tRNA-binding site and towards synergistic binders that occupy the nascent peptide exit tunnel. One of these analogues has excellent activity against several streptogramin-resistant strains of Staphylococcus aureus, exhibits decreased rates of acetylation in vitro, and is effective at lowering bacterial load in a mouse model of infection. Our results demonstrate that the combination of rational design and modular chemical synthesis can revitalize classes of antibiotics that are limited by naturally arising resistance mechanisms.
		+
		+	Synthetic group A streptogramin antibiotics that overcome Vat resistance.,Li Q, Pellegrino J, Lee DJ, Tran AA, Chaires HA, Wang R, Park JE, Ji K, Chow D, Zhang N, Brilot AF, Biel JT, van Zundert G, Borrelli K, Shinabarger D, Wolfe C, Murray B, Jacobson MP, Muhle E, Chesneau O, Fraser JS, Seiple IB Nature. 2020 Oct;586(7827):145-150. doi: 10.1038/s41586-020-2761-3. Epub 2020 Sep, 23. PMID:32968273<ref>PMID:32968273</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6pcs" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 11:25, 23 September 2020

OCA — Wed, 23 Sep 2020 11:25:07 GMT

←Older revision		Revision as of 11:25, 23 September 2020
Line 1:		Line 1:

	==E. coli 50S ribosome bound to compound 40e==		==E. coli 50S ribosome bound to compound 40e==
-	<StructureSection load='6pcs' size='340' side='right'caption='[[6pcs]]' scene=''>	+	<StructureSection load='6pcs' size='340' side='right'caption='[[6pcs]], [[Resolution\|resolution]] 2.80Å' 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=6PCS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PCS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pcs]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PCS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PCS FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6pcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pcs OCA], [http://pdbe.org/6pcs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pcs RCSB], [http://www.ebi.ac.uk/pdbsum/6pcs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pcs ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=O8S:(2R)-2-[(3S,4R,5E,10E,12E,14S,26aR)-14-hydroxy-4,12-dimethyl-1,7,16,22-tetraoxo-4,7,8,9,14,15,16,17,24,25,26,26a-dodecahydro-1H,3H,22H-21,18-(azeno)pyrrolo[2,1-c][1,8,4,19]dioxadiazacyclotetracosin-3-yl]propyl+[4-(trifluoromethyl)phenyl]carbamate'>O8S</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=1MG:1N-METHYLGUANOSINE-5-MONOPHOSPHATE'>1MG</scene>, <scene name='pdbligand=2MA:2-METHYLADENOSINE-5-MONOPHOSPHATE'>2MA</scene>, <scene name='pdbligand=2MG:2N-METHYLGUANOSINE-5-MONOPHOSPHATE'>2MG</scene>, <scene name='pdbligand=3TD:(1S)-1,4-ANHYDRO-1-(3-METHYL-2,4-DIOXO-1,2,3,4-TETRAHYDROPYRIMIDIN-5-YL)-5-O-PHOSPHONO-D-RIBITOL'>3TD</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</scene>, <scene name='pdbligand=5MU:5-METHYLURIDINE+5-MONOPHOSPHATE'>5MU</scene>, <scene name='pdbligand=6MZ:N6-METHYLADENOSINE-5-MONOPHOSPHATE'>6MZ</scene>, <scene name='pdbligand=G7M:N7-METHYL-GUANOSINE-5-MONOPHOSPHATE'>G7M</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></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6pcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pcs OCA], [http://pdbe.org/6pcs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pcs RCSB], [http://www.ebi.ac.uk/pdbsum/6pcs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pcs ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/RL3_ECOLI RL3_ECOLI]] One of two assembly inititator proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit.[HAMAP-Rule:MF_01325_B] [[http://www.uniprot.org/uniprot/A0A037Y8L6_ECOLX A0A037Y8L6_ECOLX]] Binds to the 23S rRNA.[HAMAP-Rule:MF_01341][SAAS:SAAS00124822] [[http://www.uniprot.org/uniprot/RL2_ECOLI RL2_ECOLI]] One of the primary rRNA binding proteins. Located near the base of the L1 stalk, it is probably also mobile. 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 highly controversial.[HAMAP-Rule:MF_01320_B] In the E.coli 70S ribosome in the initiation state it has been modeled to make several contacts with the 16S rRNA (forming bridge B7b, PubMed:12809609); these contacts are broken in the model with bound EF-G.[HAMAP-Rule:MF_01320_B] [[http://www.uniprot.org/uniprot/D7ZET0_ECOLX D7ZET0_ECOLX]] This protein is one of the early assembly proteins of the 50S ribosomal subunit, although it is not seen to bind rRNA by itself. It is important during the early stages of 50S assembly.[HAMAP-Rule:MF_01366][RuleBase:RU003878][SAAS:SAAS00672061] [[http://www.uniprot.org/uniprot/D7Z9F6_ECOLX D7Z9F6_ECOLX]] Forms part of the polypeptide exit tunnel.[HAMAP-Rule:MF_01328] One of the primary rRNA binding proteins, this protein initially binds near the 5'-end of the 23S rRNA. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome.[HAMAP-Rule:MF_01328]
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Escherichia coli]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Fraser JS]]	+	[[Category: Fraser, J S]]
-	[[Category: Lee DJ]]	+	[[Category: Lee, D J]]
-	[[Category: Pellegrino J]]	+	[[Category: Pellegrino, J]]
-	[[Category: Seiple IB]]	+	[[Category: Seiple, I B]]
		+	[[Category: Antibiotic]]
		+	[[Category: E. coli ribosome]]
		+	[[Category: Ribosome]]
		+	[[Category: Streptogramin a analog]]

OCA at 10:09, 17 June 2020

OCA — Wed, 17 Jun 2020 10:09:52 GMT

←Older revision		Revision as of 10:09, 17 June 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6pcs ~~is ON HOLD until Paper Publication~~	+	==E. coli 50S ribosome bound to compound 40e==
-		+	<StructureSection load='6pcs' size='340' side='right'caption='[[6pcs]]' scene=''>
-	~~Authors~~: ~~Pellegrino~~, J., ~~Lee~~, D.J., ~~Fraser, J~~.S., ~~Seiple, I~~.B.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PCS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PCS FirstGlance]. <br>
-	~~Description: E. coli 50S ribosome bound to compound 40e~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6pcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pcs OCA], [http://pdbe.org/6pcs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pcs RCSB], [http://www.ebi.ac.uk/pdbsum/6pcs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pcs ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Fraser~~, J.S~~]]	+	__TOC__
-	[[Category: ~~Pellegrino, J~~]]	+	</StructureSection>
-	[[Category: ~~Seiple, I.B~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Lee, D.J~~]]	+	[[Category: Fraser JS]]
		+	[[Category: Lee DJ]]
		+	[[Category: Pellegrino J]]
		+	[[Category: Seiple IB]]

OCA at 04:36, 27 May 2020

OCA — Wed, 27 May 2020 04:36:34 GMT

←Older revision		Revision as of 04:36, 27 May 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6pcs is ON HOLD	+	The entry 6pcs is ON HOLD until Paper Publication

	Authors: Pellegrino, J., Lee, D.J., Fraser, J.S., Seiple, I.B.		Authors: Pellegrino, J., Lee, D.J., Fraser, J.S., Seiple, I.B.
Line 7:		Line 7:
	Description: E. coli 50S ribosome bound to compound 40e		Description: E. coli 50S ribosome bound to compound 40e
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Seiple, I.B]]
-	[[Category: Lee, D.J]]
	[[Category: Fraser, J.S]]		[[Category: Fraser, J.S]]
	[[Category: Pellegrino, J]]		[[Category: Pellegrino, J]]
		+	[[Category: Seiple, I.B]]
		+	[[Category: Lee, D.J]]

OCA: Protected "6pcs" [edit=sysop:move=sysop]

OCA — Wed, 26 Jun 2019 05:17:28 GMT

Protected "6pcs" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:17, 26 June 2019

OCA: New page: '''Unreleased structure''' The entry 6pcs is ON HOLD Authors: Pellegrino, J., Lee, D.J., Fraser, J.S., Seiple, I.B. Description: E. coli 50S ribosome bound to compound 40e [[Category: ...

OCA — Wed, 26 Jun 2019 05:17:26 GMT

New page: '''Unreleased structure''' The entry 6pcs is ON HOLD Authors: Pellegrino, J., Lee, D.J., Fraser, J.S., Seiple, I.B. Description: E. coli 50S ribosome bound to compound 40e [[Category: ...

New page

'''Unreleased structure'''

The entry 6pcs is ON HOLD

Authors: Pellegrino, J., Lee, D.J., Fraser, J.S., Seiple, I.B.

Description: E. coli 50S ribosome bound to compound 40e
[[Category: Unreleased Structures]]
[[Category: Seiple, I.B]]
[[Category: Lee, D.J]]
[[Category: Fraser, J.S]]
[[Category: Pellegrino, J]]