6d4t - Revision history

OCA at 15:18, 4 October 2023

OCA — Wed, 04 Oct 2023 15:18:10 GMT

←Older revision		Revision as of 15:18, 4 October 2023
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	<StructureSection load='6d4t' size='340' side='right'caption='[[6d4t]], [[Resolution\|resolution]] 1.54Å' scene=''>		<StructureSection load='6d4t' size='340' side='right'caption='[[6d4t]], [[Resolution\|resolution]] 1.54Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6d4t]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Myct3 Myct3~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D4T OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6D4T FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6d4t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_thermoresistibile_ATCC_19527 Mycolicibacterium thermoresistibile ATCC 19527]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D4T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D4T FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FWS:(2S)-N-(2H-1,3-benzodioxol-5-yl)-4-[(isoquinolin-5-yl)sulfonyl]-2-methylpiperazine-1-carboxamide'>FWS</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</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]] 1.54Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">guaB, KEK_23061 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1078020 MYCT3])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FWS:(2S)-N-(2H-1,3-benzodioxol-5-yl)-4-[(isoquinolin-5-yl)sulfonyl]-2-methylpiperazine-1-carboxamide'>FWS</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</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=6d4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d4t OCA], [~~http~~://pdbe.org/6d4t PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6d4t RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6d4t PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6d4t 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=6d4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d4t OCA], [https://pdbe.org/6d4t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d4t RCSB], [https://www.ebi.ac.uk/pdbsum/6d4t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d4t ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/G7CNL4_MYCT3 G7CNL4_MYCT3]] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.[HAMAP-Rule:MF_01964]	+	[https://www.uniprot.org/uniprot/G7CNL4_MYCT3 G7CNL4_MYCT3] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.[HAMAP-Rule:MF_01964]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Myct3~~]]	+	[[Category: Mycolicibacterium thermoresistibile ATCC 19527]]
-	[[Category: Ascher~~, D B~~]]	+	[[Category: Ascher DB]]
-	[[Category: Blundell~~, T L~~]]	+	[[Category: Blundell TL]]
-	[[Category: Pacitto, A]]	+	[[Category: Pacitto A]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Fragment]]~~	+
-	~~[[Category: Impdh]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 08:49, 8 January 2020

OCA — Wed, 08 Jan 2020 08:49:23 GMT

←Older revision		Revision as of 08:49, 8 January 2020
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6d4t" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6d4t" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Inosine monophosphate dehydrogenase 3D structures\|Inosine monophosphate dehydrogenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:28, 23 May 2019

OCA — Thu, 23 May 2019 07:28:41 GMT

←Older revision		Revision as of 07:28, 23 May 2019
Line 3:		Line 3:
	<StructureSection load='6d4t' size='340' side='right'caption='[[6d4t]], [[Resolution\|resolution]] 1.54Å' scene=''>		<StructureSection load='6d4t' size='340' side='right'caption='[[6d4t]], [[Resolution\|resolution]] 1.54Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6d4t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D4T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D4T FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6d4t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myct3 Myct3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D4T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D4T FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FWS:(2S)-N-(2H-1,3-benzodioxol-5-yl)-4-[(isoquinolin-5-yl)sulfonyl]-2-methylpiperazine-1-carboxamide'>FWS</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FWS:(2S)-N-(2H-1,3-benzodioxol-5-yl)-4-[(isoquinolin-5-yl)sulfonyl]-2-methylpiperazine-1-carboxamide'>FWS</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">guaB, KEK_23061 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1078020 MYCT3])</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=6d4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d4t OCA], [http://pdbe.org/6d4t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d4t RCSB], [http://www.ebi.ac.uk/pdbsum/6d4t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d4t 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=6d4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d4t OCA], [http://pdbe.org/6d4t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d4t RCSB], [http://www.ebi.ac.uk/pdbsum/6d4t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d4t ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/G7CNL4_MYCT3 G7CNL4_MYCT3]] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.[HAMAP-Rule:MF_01964]		[[http://www.uniprot.org/uniprot/G7CNL4_MYCT3 G7CNL4_MYCT3]] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.[HAMAP-Rule:MF_01964]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tuberculosis (TB) is a major infectious disease associated increasingly with drug resistance. Thus, new anti-tubercular agents with novel mechanisms of action are urgently required for the treatment of drug-resistant TB. In prior work, we identified compound 1 (cyclohexyl(4-(isoquinolin-5-ylsulfonyl)piperazin-1-yl)methanone) and showed that its anti-tubercular activity is attributable to inhibition of inosine-5'-monophosphate dehydrogenase (IMPDH) in Mycobacterium tuberculosis. In the present study, we explored the structure-activity relationship around compound 1 by synthesizing and evaluating the inhibitory activity of analogues against M. tuberculosis IMPDH in biochemical and whole-cell assays. X-ray crystallography was performed to elucidate the mode of binding of selected analogues to IMPDH. We establish the importance of the cyclohexyl, piperazine and isoquinoline rings for activity, and report the identification of an analogue with IMPDH-selective activity against a mutant of M. tuberculosis that is highly resistant to compound 1. We also show that the nitrogen in urea analogues is required for anti-tubercular activity and identify benzylurea derivatives as promising inhibitors that warrant further investigation.
		+
		+	Synthesis and Structure-Activity relationship of 1-(5-isoquinolinesulfonyl)piperazine analogues as inhibitors of Mycobacterium tuberculosis IMPDH.,Singh V, Pacitto A, Donini S, Ferraris DM, Boros S, Illyes E, Szokol B, Rizzi M, Blundell TL, Ascher DB, Pato J, Mizrahi V Eur J Med Chem. 2019 Jul 15;174:309-329. doi: 10.1016/j.ejmech.2019.04.027. Epub , 2019 Apr 15. PMID:31055147<ref>PMID:31055147</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6d4t" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Myct3]]
	[[Category: Ascher, D B]]		[[Category: Ascher, D B]]
	[[Category: Blundell, T L]]		[[Category: Blundell, T L]]

OCA at 08:43, 1 May 2019

OCA — Wed, 01 May 2019 08:43:27 GMT

←Older revision		Revision as of 08:43, 1 May 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6d4t is ~~ON HOLD until Paper Publication~~	+	==M. thermoresistible GuaB2 delta-CBS in complex with inhibitor Compound 45 (VCC117054)==
-		+	<StructureSection load='6d4t' size='340' side='right'caption='[[6d4t]], [[Resolution\|resolution]] 1.54Å' scene=''>
-	~~Authors~~: ~~Ascher~~, D.B., ~~Pacitto~~, A., ~~Blundell~~, T.L.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6d4t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D4T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D4T FirstGlance]. <br>
-	~~Description~~: M. ~~thermoresistible GuaB2 delta~~-~~CBS in complex with inhibitor Compound 45~~ (~~VCC117054~~)	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FWS:(2S)-N-(2H-1,3-benzodioxol-5-yl)-4-[(isoquinolin-5-yl)sulfonyl]-2-methylpiperazine-1-carboxamide'>FWS</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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=6d4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d4t OCA], [http://pdbe.org/6d4t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d4t RCSB], [http://www.ebi.ac.uk/pdbsum/6d4t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d4t ProSAT]</span></td></tr>
-	[[Category: ~~Blundell~~, ~~T.L~~]]	+	</table>
-	[[Category: ~~Ascher~~, ~~D.B~~]]	+	== Function ==
		+	[[http://www.uniprot.org/uniprot/G7CNL4_MYCT3 G7CNL4_MYCT3]] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.[HAMAP-Rule:MF_01964]
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Ascher, D B]]
		+	[[Category: Blundell, T L]]
	[[Category: Pacitto, A]]		[[Category: Pacitto, A]]
		+	[[Category: Complex]]
		+	[[Category: Fragment]]
		+	[[Category: Impdh]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 04:39, 24 April 2019

OCA — Wed, 24 Apr 2019 04:39:31 GMT

←Older revision		Revision as of 04:39, 24 April 2019
Line 5:		Line 5:
	Authors: Ascher, D.B., Pacitto, A., Blundell, T.L.		Authors: Ascher, D.B., Pacitto, A., Blundell, T.L.

-	Description: M. thermoresistible GuaB2 delta-CBS in complex with inhibitor Compound 48 (VCC117054)	+	Description: M. thermoresistible GuaB2 delta-CBS in complex with inhibitor Compound 45 (VCC117054)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Blundell, T.L]]		[[Category: Blundell, T.L]]
	[[Category: Ascher, D.B]]		[[Category: Ascher, D.B]]
	[[Category: Pacitto, A]]		[[Category: Pacitto, A]]

OCA at 08:39, 5 September 2018

OCA — Wed, 05 Sep 2018 08:39:55 GMT

←Older revision		Revision as of 08:39, 5 September 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6d4t is ON HOLD	+	The entry 6d4t is ON HOLD until Paper Publication

	Authors: Ascher, D.B., Pacitto, A., Blundell, T.L.		Authors: Ascher, D.B., Pacitto, A., Blundell, T.L.

OCA: Protected "6d4t" [edit=sysop:move=sysop]

OCA — Wed, 25 Apr 2018 04:12:30 GMT

Protected "6d4t" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:12, 25 April 2018

OCA: New page: '''Unreleased structure''' The entry 6d4t is ON HOLD Authors: Ascher, D.B., Pacitto, A., Blundell, T.L. Description: M. thermoresistible GuaB2 delta-CBS in complex with inhibitor Compo...

OCA — Wed, 25 Apr 2018 04:12:29 GMT

New page: '''Unreleased structure''' The entry 6d4t is ON HOLD Authors: Ascher, D.B., Pacitto, A., Blundell, T.L. Description: M. thermoresistible GuaB2 delta-CBS in complex with inhibitor Compo...

New page

'''Unreleased structure'''

The entry 6d4t is ON HOLD

Authors: Ascher, D.B., Pacitto, A., Blundell, T.L.

Description: M. thermoresistible GuaB2 delta-CBS in complex with inhibitor Compound 48 (VCC117054)
[[Category: Unreleased Structures]]
[[Category: Blundell, T.L]]
[[Category: Ascher, D.B]]
[[Category: Pacitto, A]]