4unn - Revision history

OCA at 10:31, 10 January 2024

OCA — Wed, 10 Jan 2024 10:31:16 GMT

←Older revision		Revision as of 10:31, 10 January 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4unn]] is a 2 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=4UNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UNN FirstGlance]. <br>		<table><tr><td colspan='2'>[[4unn]] is a 2 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=4UNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UNN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QZZ:4-[3-CYANO-6-(3-METHOXYPHENYL)-2-OXO-1H-PYRIDIN-4-YL]BENZOIC+ACID'>QZZ</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]] 2.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QZZ:4-[3-CYANO-6-(3-METHOXYPHENYL)-2-OXO-1H-PYRIDIN-4-YL]BENZOIC+ACID'>QZZ</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=4unn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4unn OCA], [https://pdbe.org/4unn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4unn RCSB], [https://www.ebi.ac.uk/pdbsum/4unn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4unn 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=4unn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4unn OCA], [https://pdbe.org/4unn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4unn RCSB], [https://www.ebi.ac.uk/pdbsum/4unn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4unn ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:27, 29 March 2023

OCA — Wed, 29 Mar 2023 07:27:24 GMT

←Older revision		Revision as of 07:27, 29 March 2023
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	<StructureSection load='4unn' size='340' side='right'caption='[[4unn]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4unn' size='340' side='right'caption='[[4unn]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4unn]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus~~ tuberculosis~~" (zopf 1883) klein 1884~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UNN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4UNN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4unn]] is a 2 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=4UNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UNN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=QZZ:4-[3-CYANO-6-(3-METHOXYPHENYL)-2-OXO-1H-PYRIDIN-4-YL]BENZOIC+ACID'>QZZ</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QZZ:4-[3-CYANO-6-(3-METHOXYPHENYL)-2-OXO-1H-PYRIDIN-4-YL]BENZOIC+ACID'>QZZ</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </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=4unn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4unn OCA], [https://pdbe.org/4unn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4unn RCSB], [https://www.ebi.ac.uk/pdbsum/4unn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4unn ProSAT]</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=4unn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4unn OCA], [~~http~~://pdbe.org/4unn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4unn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4unn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4unn ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/KTHY_MYCTU KTHY_MYCTU] Catalyzes the reversible phosphorylation of deoxythymidine monophosphate (dTMP) to deoxythymidine diphosphate (dTDP), using ATP as its preferred phosphoryl donor. Situated at the junction of both de novo and salvage pathways of deoxythymidine triphosphate (dTTP) synthesis, is essential for DNA synthesis and cellular growth. Has a broad specificity for nucleoside triphosphates, being highly active with ATP or dATP as phosphate donors, and less active with ITP, GTP, CTP and UTP.[HAMAP-Rule:MF_00165]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
-	*[[Thymidylate kinase\|Thymidylate kinase]]	+	*[[Thymidylate kinase 3D structures\|Thymidylate kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~DTMP kinase~~]]	+	[[Category: Mycobacterium tuberculosis]]
-	[[Category: Gingell, H]]	+	[[Category: Gingell H]]
-	[[Category: Hussein, S]]	+	[[Category: Hussein S]]
-	[[Category: Read~~, J A~~]]	+	[[Category: Read JA]]
-	[[Category: Tucker, J]]	+	[[Category: Tucker J]]
-	~~[[Category: Atp tmp phosphotransferase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:50, 21 May 2019

OCA — Tue, 21 May 2019 08:50:04 GMT

←Older revision		Revision as of 08:50, 21 May 2019
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	==Mtb TMK in complex with compound 8==		==Mtb TMK in complex with compound 8==
-	<StructureSection load='4unn' size='340' side='right' caption='[[4unn]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='4unn' size='340' side='right'caption='[[4unn]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4unn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UNN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UNN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4unn]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UNN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UNN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=QZZ:4-[3-CYANO-6-(3-METHOXYPHENYL)-2-OXO-1H-PYRIDIN-4-YL]BENZOIC+ACID'>QZZ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=QZZ:4-[3-CYANO-6-(3-METHOXYPHENYL)-2-OXO-1H-PYRIDIN-4-YL]BENZOIC+ACID'>QZZ</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </span></td></tr>
Line 24:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: DTMP kinase]]		[[Category: DTMP kinase]]
	[[Category: Gingell, H]]		[[Category: Gingell, H]]

OCA at 14:17, 27 April 2017

OCA — Thu, 27 Apr 2017 14:17:46 GMT

←Older revision		Revision as of 14:17, 27 April 2017
Line 1:		Line 1:
		+
	==Mtb TMK in complex with compound 8==		==Mtb TMK in complex with compound 8==
	<StructureSection load='4unn' size='340' side='right' caption='[[4unn]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4unn' size='340' side='right' caption='[[4unn]], [[Resolution\|resolution]] 2.50Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=QZZ:4-[3-CYANO-6-(3-METHOXYPHENYL)-2-OXO-1H-PYRIDIN-4-YL]BENZOIC+ACID'>QZZ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=QZZ:4-[3-CYANO-6-(3-METHOXYPHENYL)-2-OXO-1H-PYRIDIN-4-YL]BENZOIC+ACID'>QZZ</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </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=4unn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4unn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4unn RCSB], [http://www.ebi.ac.uk/pdbsum/4unn PDBsum]</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=4unn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4unn OCA], [http://pdbe.org/4unn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4unn RCSB], [http://www.ebi.ac.uk/pdbsum/4unn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4unn ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4unn" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Thymidylate kinase\|Thymidylate kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:08, 22 July 2015

OCA — Wed, 22 Jul 2015 08:08:16 GMT

←Older revision		Revision as of 08:08, 22 July 2015
Line 7:		Line 7:
	<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=4unn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4unn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4unn RCSB], [http://www.ebi.ac.uk/pdbsum/4unn PDBsum]</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=4unn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4unn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4unn RCSB], [http://www.ebi.ac.uk/pdbsum/4unn PDBsum]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	M. tuberculosis thymidylate kinase (Mtb TMK) has been shown in vitro to be an essential enzyme in DNA synthesis. In order to identify novel leads for Mtb TMK, we performed a high throughput biochemical screen and an NMR based fragment screen through which we discovered two novel classes of inhibitors, 3-cyanopyridones and 1,6-naphthyridin-2-ones, respectively. We describe three cyanopyridone subseries that arose during our hit to lead campaign, along with cocrystal structures of representatives with Mtb TMK. Structure aided optimization of the cyanopyridones led to single digit nanomolar inhibitors of Mtb TMK. Fragment based lead generation, augmented by crystal structures and the SAR from the cyanopyridones, enabled us to drive the potency of our 1,6-naphthyridin-2-one fragment hit from 500 muM to 200 nM while simultaneously improving the ligand efficiency. Cyanopyridone derivatives containing sulfoxides and sulfones showed cellular activity against M. tuberculosis. To the best of our knowledge, these compounds are the first reports of non-thymidine-like inhibitors of Mtb TMK.
		+
		+	Structure guided lead generation for M. tuberculosis thymidylate kinase (Mtb TMK): discovery of 3-cyanopyridone and 1,6-naphthyridin-2-one as potent inhibitors.,Naik M, Raichurkar A, Bandodkar BS, Varun BV, Bhat S, Kalkhambkar R, Murugan K, Menon R, Bhat J, Paul B, Iyer H, Hussein S, Tucker JA, Vogtherr M, Embrey KJ, McMiken H, Prasad S, Gill A, Ugarkar BG, Venkatraman J, Read J, Panda M J Med Chem. 2015 Jan 22;58(2):753-66. doi: 10.1021/jm5012947. Epub 2014 Dec 23. PMID:25486447<ref>PMID:25486447</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 15:21, 17 June 2015

OCA — Wed, 17 Jun 2015 15:21:56 GMT

←Older revision		Revision as of 15:21, 17 June 2015
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Mtb TMK in complex with compound 8==
-		+	<StructureSection load='4unn' size='340' side='right' caption='[[4unn]], [[Resolution\|resolution]] 2.50Å' scene=''>
-	~~The entry~~ 4unn is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4unn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UNN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UNN FirstGlance]. <br>
-	~~Authors~~: ~~Read~~, J.A., ~~Hussein, S~~., ~~Gingell, H~~., ~~Tucker, J~~.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=QZZ:4-[3-CYANO-6-(3-METHOXYPHENYL)-2-OXO-1H-PYRIDIN-4-YL]BENZOIC+ACID'>QZZ</scene></td></tr>
-		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </span></td></tr>
-	~~Description~~: ~~Mtb TMK in complex with compound 8~~	+	<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=4unn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4unn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4unn RCSB], [http://www.ebi.ac.uk/pdbsum/4unn PDBsum]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: DTMP kinase]]
		+	[[Category: Gingell, H]]
	[[Category: Hussein, S]]		[[Category: Hussein, S]]
		+	[[Category: Read, J A]]
	[[Category: Tucker, J]]		[[Category: Tucker, J]]
-	[[Category: ~~Read, J.A~~]]	+	[[Category: Atp tmp phosphotransferase]]
-	[[Category: ~~Gingell, H~~]]	+	[[Category: Transferase]]

OCA at 18:32, 24 December 2014

OCA — Wed, 24 Dec 2014 18:32:54 GMT

←Older revision		Revision as of 18:32, 24 December 2014
Line 6:		Line 6:

	Description: Mtb TMK in complex with compound 8		Description: Mtb TMK in complex with compound 8
		+	[[Category: Unreleased Structures]]
		+	[[Category: Hussein, S]]
		+	[[Category: Tucker, J]]
		+	[[Category: Read, J.A]]
		+	[[Category: Gingell, H]]

OCA: Protected "4unn" [edit=sysop:move=sysop]

OCA — Wed, 04 Jun 2014 05:00:53 GMT

Protected "4unn" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:00, 4 June 2014

OCA: New page: '''Unreleased structure''' The entry 4unn is ON HOLD until Paper Publication Authors: Read, J.A., Hussein, S., Gingell, H., Tucker, J. Description: Mtb TMK in complex with compound 8

OCA — Wed, 04 Jun 2014 05:00:52 GMT

New page: '''Unreleased structure''' The entry 4unn is ON HOLD until Paper Publication Authors: Read, J.A., Hussein, S., Gingell, H., Tucker, J. Description: Mtb TMK in complex with compound 8

New page

'''Unreleased structure'''

The entry 4unn is ON HOLD until Paper Publication

Authors: Read, J.A., Hussein, S., Gingell, H., Tucker, J.

Description: Mtb TMK in complex with compound 8