7ev2 - Revision history

OCA at 17:04, 29 November 2023

2023-11-29T17:04:44Z

← Older revision		Revision as of 17:04, 29 November 2023
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	==Crystal structure of Mycobacterium tuberculosis tryptophanyl-tRNA synthetase complexed with Y-11 and ATP==		==Crystal structure of Mycobacterium tuberculosis tryptophanyl-tRNA synthetase complexed with Y-11 and ATP==
	<StructureSection load='7ev2' size='340' side='right'caption='[[7ev2]]' scene=''>		<StructureSection load='7ev2' size='340' side='right'caption='[[7ev2]], [[Resolution\|resolution]] 2.10Å' 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=7EV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EV2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7ev2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EV2 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=7ev2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ev2 OCA], [https://pdbe.org/7ev2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ev2 RCSB], [https://www.ebi.ac.uk/pdbsum/7ev2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ev2 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]] 2.1Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=JE0:(5S)-5-[(1R)-1-(4-chloranyl-1H-indol-3-yl)ethyl]-2-(methylamino)-1,3-oxazol-4-one'>JE0</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7ev2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ev2 OCA], [https://pdbe.org/7ev2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ev2 RCSB], [https://www.ebi.ac.uk/pdbsum/7ev2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ev2 ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/SYW_MYCTU SYW_MYCTU]
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Indolmycin (IND) is a microbial natural product that selectively inhibits bacterial tryptophanyl-tRNA synthetase (TrpRS). The tryptophan biosynthesis pathway was recently shown to be an important target for developing new antibacterial agents against Mycobacterium tuberculosis (Mtb). We investigated the antibacterial activity of IND against several mycobacterial model strains. A TrpRS biochemical assay was developed to analyze a library of synthetic IND analogues. The 4''-methylated IND compound, Y-13, showed improved anti-Mtb activity with a minimum inhibitory concentration (MIC) of 1.88 muM ( approximately 0.5 mug/mL). The MIC increased significantly when overexpression of TrpRS was induced in the genetically engineered surrogate M. bovis BCG. The cocrystal structure of Mtb TrpRS complexed with IND and ATP has revealed that the amino acid pocket is in a state between the open form of apo protein and the closed complex with the reaction intermediate. In whole-cell-based experiments, we studied the combination effect of Y-13 paired with different antibacterial agents. We evaluated the killing kinetics, the frequency of resistance to INDs, and the mode of resistance of IND-resistant mycobacteria by genome sequencing. The synergistic interaction of Y-13 with the TrpE allosteric inhibitor, indole propionic acid, suggests that prospective IND analogues could shut down tryptophan biosynthesis and protein biosynthesis in pathogens, leading to a new class of antibiotics. Finally, we discuss a strategy to expand the genome mining of antibiotic-producing microbes specifically for antimycobacterial development.

			Investigate Natural Product Indolmycin and the Synthetically Improved Analogue Toward Antimycobacterial Agents.,Yang Y, Xu Y, Yue Y, Wang H, Cui Y, Pan M, Zhang X, Zhang L, Li H, Xu M, Tang Y, Chen S ACS Chem Biol. 2022 Jan 21;17(1):39-53. doi: 10.1021/acschembio.1c00394. Epub, 2021 Dec 15. PMID:34908399<ref>PMID:34908399</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7ev2" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Aminoacyl tRNA synthetase 3D structures\|Aminoacyl tRNA synthetase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
			[[Category: Mycobacterium tuberculosis]]
	[[Category: Chen S]]		[[Category: Chen S]]
	[[Category: Xu M]]		[[Category: Xu M]]

OCA at 10:15, 16 February 2022

2022-02-16T10:15:09Z

← Older revision		Revision as of 10:15, 16 February 2022
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	~~'''Unreleased structure'''~~

	~~The entry 7ev2 is ON HOLD until Paper Publication~~		==Crystal structure of Mycobacterium tuberculosis tryptophanyl-tRNA synthetase complexed with Y-11 and ATP==
			<StructureSection load='7ev2' size='340' side='right'caption='[[7ev2]]' scene=''>
	~~Authors: Xu, M., Chen, S.~~		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EV2 FirstGlance]. <br>
	~~Description:~~ Crystal structure of Mycobacterium tuberculosis tryptophanyl-tRNA synthetase complexed with Y-11 and ATP		</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=7ev2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ev2 OCA], [https://pdbe.org/7ev2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ev2 RCSB], [https://www.ebi.ac.uk/pdbsum/7ev2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ev2 ProSAT]</span></td></tr>
	[[Category: ~~Unreleased~~ Structures]]		</table>
	[[Category: Chen, S]]		__TOC__
	[[Category: Xu, M]]		</StructureSection>
			[[Category: Large Structures]]
			[[Category: Chen S]]
			[[Category: Xu M]]

OCA at 13:30, 17 June 2021

2021-06-17T13:30:17Z

← Older revision		Revision as of 13:30, 17 June 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7ev2 is ON HOLD		The entry 7ev2 is ON HOLD until Paper Publication

	Authors: Xu, M., Chen, S.		Authors: Xu, M., Chen, S.

OCA: Protected "7ev2" [edit=sysop:move=sysop]

2021-05-26T07:52:18Z

Protected "7ev2" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:52, 26 May 2021
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7ev2 is ON HOLD Authors: Xu, M., Chen, S. Description: Crystal structure of Mycobacterium tuberculosis tryptophanyl-tRNA synthetase complexed with ...

2021-05-26T07:52:17Z

New page: '''Unreleased structure''' The entry 7ev2 is ON HOLD Authors: Xu, M., Chen, S. Description: Crystal structure of Mycobacterium tuberculosis tryptophanyl-tRNA synthetase complexed with ...

New page

'''Unreleased structure'''

The entry 7ev2 is ON HOLD

Authors: Xu, M., Chen, S.

Description: Crystal structure of Mycobacterium tuberculosis tryptophanyl-tRNA synthetase complexed with Y-11 and ATP
[[Category: Unreleased Structures]]
[[Category: Chen, S]]
[[Category: Xu, M]]