5zhk - Revision history

OCA at 08:55, 22 November 2023

OCA — Wed, 22 Nov 2023 08:55:12 GMT

←Older revision		Revision as of 08:55, 22 November 2023
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	==Crystal structure of TrmD from Mycobacterium tuberculosis in complex with active-site inhibitor==		==Crystal structure of TrmD from Mycobacterium tuberculosis in complex with active-site inhibitor==
-	<StructureSection load='5zhk' size='340' side='right' caption='[[5zhk]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='5zhk' size='340' side='right'caption='[[5zhk]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5zhk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZHK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ZHK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5zhk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZHK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZHK FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=9D6:N~~-[~~(4-{~~[~~cyclohexyl(ethyl)amino~~]~~methyl}phenyl)methyl~~]~~-4-oxo-3,4-dihydrothieno[~~2,3~~-d]pyrimidine-5-carboxamide'>9D6</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]] 2.3Å</td></tr>
-	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks'>[http~~:~~//en.wikipedia.org/wiki/tRNA_(guanine(37)-~~N~~(1))~~-~~methyltransferase tRNA~~ (~~guanine(37)~~-N(1))-~~methyltransferase]~~, ~~with EC number~~ [~~http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=2.1.1.228 2.1.1.228~~] </~~span~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9D6:N-[(4-{[cyclohexyl(ethyl)amino]methyl}phenyl)methyl]-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-5-carboxamide'>9D6</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5zhk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zhk OCA], [~~http~~://pdbe.org/5zhk PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5zhk RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5zhk PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5zhk ProSAT]</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=5zhk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zhk OCA], [https://pdbe.org/5zhk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zhk RCSB], [https://www.ebi.ac.uk/pdbsum/5zhk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zhk ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TRMD_MYCTU TRMD_MYCTU]] Specifically methylates guanosine-37 in various tRNAs.	+	[https://www.uniprot.org/uniprot/TRMD_MYCTU TRMD_MYCTU] Specifically methylates guanosine-37 in various tRNAs.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Among the >120 modified ribonucleosides in the prokaryotic epitranscriptome, many tRNA modifications are critical to bacterial survival, which makes their synthetic enzymes ideal targets for antibiotic development. Here we performed a structure-based design of inhibitors of tRNA-(N(1)G37) methyltransferase, TrmD, which is an essential enzyme in many bacterial pathogens. On the basis of crystal structures of TrmDs from Pseudomonas aeruginosa and Mycobacterium tuberculosis, we synthesized a series of thienopyrimidinone derivatives with nanomolar potency against TrmD in vitro and discovered a novel active site conformational change triggered by inhibitor binding. This tyrosine-flipping mechanism is uniquely found in P. aeruginosa TrmD and renders the enzyme inaccessible to the cofactor S-adenosyl-l-methionine (SAM) and probably to the substrate tRNA. Biophysical and biochemical structure-activity relationship studies provided insights into the mechanisms underlying the potency of thienopyrimidinones as TrmD inhibitors, with several derivatives found to be active against Gram-positive and mycobacterial pathogens. These results lay a foundation for further development of TrmD inhibitors as antimicrobial agents.
		+
		+	Thienopyrimidinone Derivatives That Inhibit Bacterial tRNA (Guanine37-N(1))-Methyltransferase (TrmD) by Restructuring the Active Site with a Tyrosine-Flipping Mechanism.,Zhong W, Pasunooti KK, Balamkundu S, Wong YH, Nah Q, Gadi V, Gnanakalai S, Chionh YH, McBee ME, Gopal P, Lim SH, Olivier N, Buurman ET, Dick T, Liu CF, Lescar J, Dedon PC J Med Chem. 2019 Sep 12;62(17):7788-7805. doi: 10.1021/acs.jmedchem.9b00582. Epub , 2019 Aug 29. PMID:31442049<ref>PMID:31442049</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5zhk" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[TRNA methyltransferase 3D structures\|TRNA methyltransferase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Balamkundu, S~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Dedon, P C~~]]	+	[[Category: Mycobacterium tuberculosis H37Rv]]
-	[[Category: ~~Lescar, J~~]]	+	[[Category: Balamkundu S]]
-	[[Category: ~~Liu, C F~~]]	+	[[Category: Dedon PC]]
-	[[Category: ~~Nah, Q~~]]	+	[[Category: Lescar J]]
-	[[Category: ~~Pasunooti, K K~~]]	+	[[Category: Liu CF]]
-	[[Category: ~~Wong, Y W~~]]	+	[[Category: Nah Q]]
-	[[Category: ~~Zhong, W~~]]	+	[[Category: Pasunooti KK]]
-	[[Category: ~~Transferase~~]]	+	[[Category: Wong YW]]
-	[[Category: ~~Trna methyltransferase~~]]	+	[[Category: Zhong W]]

OCA at 07:23, 6 March 2019

OCA — Wed, 06 Mar 2019 07:23:10 GMT

←Older revision		Revision as of 07:23, 6 March 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5zhk ~~is ON HOLD~~ ~~until Paper Publication~~	+	==Crystal structure of TrmD from Mycobacterium tuberculosis in complex with active-site inhibitor==
-		+	<StructureSection load='5zhk' size='340' side='right' caption='[[5zhk]], [[Resolution\|resolution]] 2.30Å' scene=''>
-	~~Authors~~: ~~Zhong, W~~., ~~Pasunooti~~, K.K., ~~Balamkundu, S~~.~~, Wong, Y~~.W., ~~Nah~~, Q., ~~Liu, C~~.F., ~~Lescar, J~~., ~~Dedon, P~~.C.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5zhk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZHK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZHK FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of TrmD from Mycobacterium tuberculosis in complex with active~~-~~site inhibitor~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9D6:N-[(4-{[cyclohexyl(ethyl)amino]methyl}phenyl)methyl]-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-5-carboxamide'>9D6</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/tRNA_(guanine(37)-N(1))-methyltransferase tRNA (guanine(37)-N(1))-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.228 2.1.1.228] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5zhk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zhk OCA], [http://pdbe.org/5zhk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zhk RCSB], [http://www.ebi.ac.uk/pdbsum/5zhk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zhk ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TRMD_MYCTU TRMD_MYCTU]] Specifically methylates guanosine-37 in various tRNAs.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Balamkundu, S]]
		+	[[Category: Dedon, P C]]
	[[Category: Lescar, J]]		[[Category: Lescar, J]]
-	~~[[Category: Balamkundu, S]]~~	+	[[Category: Liu, C F]]
-	~~[[Category: Pasunooti, K.K]]~~	+
-	~~[[Category: Wong, Y.W]]~~	+
-	[[Category: Liu, C.F]]	+
	[[Category: Nah, Q]]		[[Category: Nah, Q]]
-	[[Category: ~~Dedon~~, ~~P.C~~]]	+	[[Category: Pasunooti, K K]]
		+	[[Category: Wong, Y W]]
	[[Category: Zhong, W]]		[[Category: Zhong, W]]
		+	[[Category: Transferase]]
		+	[[Category: Trna methyltransferase]]

OCA at 04:29, 4 April 2018

OCA — Wed, 04 Apr 2018 04:29:47 GMT

←Older revision		Revision as of 04:29, 4 April 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5zhk is ON HOLD	+	The entry 5zhk is ON HOLD until Paper Publication

	Authors: Zhong, W., Pasunooti, K.K., Balamkundu, S., Wong, Y.W., Nah, Q., Liu, C.F., Lescar, J., Dedon, P.C.		Authors: Zhong, W., Pasunooti, K.K., Balamkundu, S., Wong, Y.W., Nah, Q., Liu, C.F., Lescar, J., Dedon, P.C.

OCA: Protected "5zhk" [edit=sysop:move=sysop]

OCA — Wed, 21 Mar 2018 06:00:57 GMT

Protected "5zhk" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:00, 21 March 2018

OCA: New page: '''Unreleased structure''' The entry 5zhk is ON HOLD Authors: Zhong, W., Pasunooti, K.K., Balamkundu, S., Wong, Y.W., Nah, Q., Liu, C.F., Lescar, J., Dedon, P.C. Description: Crystal s...

OCA — Wed, 21 Mar 2018 06:00:56 GMT

New page: '''Unreleased structure''' The entry 5zhk is ON HOLD Authors: Zhong, W., Pasunooti, K.K., Balamkundu, S., Wong, Y.W., Nah, Q., Liu, C.F., Lescar, J., Dedon, P.C. Description: Crystal s...

New page

'''Unreleased structure'''

The entry 5zhk is ON HOLD

Authors: Zhong, W., Pasunooti, K.K., Balamkundu, S., Wong, Y.W., Nah, Q., Liu, C.F., Lescar, J., Dedon, P.C.

Description: Crystal structure of TrmD from Mycobacterium tuberculosis in complex with active-site inhibitor
[[Category: Unreleased Structures]]
[[Category: Lescar, J]]
[[Category: Balamkundu, S]]
[[Category: Pasunooti, K.K]]
[[Category: Wong, Y.W]]
[[Category: Liu, C.F]]
[[Category: Nah, Q]]
[[Category: Dedon, P.C]]
[[Category: Zhong, W]]