5c9x - Revision history

OCA at 08:36, 27 September 2023

OCA — Wed, 27 Sep 2023 08:36:15 GMT

←Older revision		Revision as of 08:36, 27 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5c9x]] 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=5C9X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C9X FirstGlance]. <br>		<table><tr><td colspan='2'>[[5c9x]] 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=5C9X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C9X FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4Z4:2,4-DICHLORO-5-FLUOROBENZOIC+ACID'>4Z4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.1Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4Z4:2,4-DICHLORO-5-FLUOROBENZOIC+ACID'>4Z4</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=5c9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c9x OCA], [https://pdbe.org/5c9x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c9x RCSB], [https://www.ebi.ac.uk/pdbsum/5c9x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c9x 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=5c9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c9x OCA], [https://pdbe.org/5c9x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c9x RCSB], [https://www.ebi.ac.uk/pdbsum/5c9x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c9x ProSAT]</span></td></tr>
	</table>		</table>

OCA at 06:25, 7 June 2023

OCA — Wed, 07 Jun 2023 06:25:52 GMT

←Older revision		Revision as of 06:25, 7 June 2023
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	<StructureSection load='5c9x' size='340' side='right'caption='[[5c9x]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='5c9x' size='340' side='right'caption='[[5c9x]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5c9x]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C9X OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5C9X FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5c9x]] 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=5C9X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C9X FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4Z4:2,4-DICHLORO-5-FLUOROBENZOIC+ACID'>4Z4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4Z4:2,4-DICHLORO-5-FLUOROBENZOIC+ACID'>4Z4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Malate_synthase Malate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.9 2.3.3.9] </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=5c9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c9x OCA], [https://pdbe.org/5c9x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c9x RCSB], [https://www.ebi.ac.uk/pdbsum/5c9x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c9x 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=5c9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c9x OCA], [~~http~~://pdbe.org/5c9x PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5c9x RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5c9x PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5c9x ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MASZ_MYCTU MASZ_MYCTU]] Involved in the glycolate utilization. Catalyzes the condensation and subsequent hydrolysis of acetyl-coenzyme A (acetyl-CoA) and glyoxylate to form malate and CoA (By similarity).[HAMAP-Rule:MF_00641]	+	[https://www.uniprot.org/uniprot/MASZ_MYCTU MASZ_MYCTU] Involved in the glycolate utilization. Catalyzes the condensation and subsequent hydrolysis of acetyl-coenzyme A (acetyl-CoA) and glyoxylate to form malate and CoA (By similarity).[HAMAP-Rule:MF_00641]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Malate synthase~~]]	+	[[Category: Mycobacterium tuberculosis H37Rv]]
-	[[Category: Huang, H L]]	+	[[Category: Huang H-L]]
-	[[Category: Sacchettini~~, J C]]~~	+	[[Category: Sacchettini JC]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Fragment]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 11:29, 27 March 2020

OCA — Fri, 27 Mar 2020 11:29:23 GMT

←Older revision		Revision as of 11:29, 27 March 2020
Line 1:		Line 1:

	==Crystal structure of Mycobacterium tuberculosis malate synthase in complex with 2,4-dichloro-5-fluorobenzoic acid==		==Crystal structure of Mycobacterium tuberculosis malate synthase in complex with 2,4-dichloro-5-fluorobenzoic acid==
-	<StructureSection load='5c9x' size='340' side='right' caption='[[5c9x]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='5c9x' size='340' side='right'caption='[[5c9x]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5c9x]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C9X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C9X FirstGlance]. <br>		<table><tr><td colspan='2'>[[5c9x]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C9X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C9X FirstGlance]. <br>
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5c9x" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5c9x" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Malate synthase 3D structures\|Malate synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Malate synthase]]		[[Category: Malate synthase]]
	[[Category: Huang, H L]]		[[Category: Huang, H L]]

OCA at 11:22, 26 October 2016

OCA — Wed, 26 Oct 2016 11:22:40 GMT

←Older revision		Revision as of 11:22, 26 October 2016
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	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~Establishment or maintenance of a persistent infection by Mycobacterium tuberculosis requires~~ the ~~glyoxylate pathway. This is a bypass~~ of ~~the tricarboxylic acid cycle in which isocitrate lyase~~ and malate synthase (GlcB) ~~catalyze the net incorporation of carbon during growth of microorganisms on acetate or fatty acids as the primary carbon source. The glcB gene~~ from M. tuberculosis~~, which encodes malate synthase, was cloned,~~ and ~~GlcB was expressed in Escherichia coli~~. ~~The influence~~ of ~~media conditions on expression~~ in ~~M. tuberculosis~~ indicated ~~that this enzyme is regulated differentially~~ to ~~isocitrate lyase~~. ~~Purified GlcB had K~~(m) ~~values~~ of 57 and 30 microm for its substrates glyoxylate and acetyl coenzyme A, respectively, and was inhibited by bromopyruvate, oxalate, and phosphoenolpyruvate. The GlcB structure was solved to 2.1-A resolution in the ~~presence~~ of ~~glyoxylate and magnesium~~. ~~We also report the structure~~ of GlcB in complex with the ~~products~~ of the ~~reaction~~, ~~coenzyme A and malate, solved~~ to 2.7-~~A resolution. Coenzyme A binds in a bent conformation, and~~ the ~~details~~ of ~~its interactions are described, together with implications on the enzyme mechanism~~.	+	Fragment screening and high-throughput screening are complementary approaches that go hand in hand with structural biology to explore the binding capabilities of an active site and to provide diversity for inhibitor design. We used fragment-based approaches on malate synthase (GlcB) from Mycobacterium tuberculosis and discovered several novel binding chemotypes. In addition, the crystal structures of GlcB in complex with these fragments indicated conformational changes in the active site hypothesized to represent states the enzyme assumes in the substrate-product exchange during catalysis. Additional structures of the late product formation stage (in complex with malate) and of the apo form of GlcB supported that hypothesis. Comparative analysis of GlcB structures in complex with 18 fragments allowed us to characterize the preferred chemotypes and their modes of binding. The fragment structures showed a hydrogen bond to the backbone carbonyl of Met631, we successfully incorporated fragment moiety into an existing phenyl-diketo acid (PDKA) inhibitor to take advantage of this interaction. The result was 100-fold more potent than the parent PDKA indole-containing inhibitor with an IC 50 value of 20 nM.

-	~~Biochemical and structural studies of malate synthase from~~ Mycobacterium tuberculosis.~~,Smith CV~~, Huang CC, ~~Miczak A~~, ~~Russell DG~~, Sacchettini JC~~, Honer zu Bentrup K~~ J Biol Chem. ~~2003 Jan 17;278(3)~~:~~1735-43~~. ~~Epub 2002 Oct 21~~. PMID:~~12393860~~<ref>PMID:~~12393860~~</ref>	+	Mycobacterium tuberculosis Malate Synthase Structures with Fragments Reveal a Portal for Substrate/Product Exchange.,Huang HL, Krieger IV, Parai MK, Gawandi VB, Sacchettini JC J Biol Chem. 2016 Oct 13. pii: jbc.M116.750877. PMID:27738104<ref>PMID:27738104</ref>

	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>

OCA at 15:59, 10 August 2016

OCA — Wed, 10 Aug 2016 15:59:44 GMT

←Older revision		Revision as of 15:59, 10 August 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5c9x is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of Mycobacterium tuberculosis malate synthase in complex with 2,4-dichloro-5-fluorobenzoic acid==
		+	<StructureSection load='5c9x' size='340' side='right' caption='[[5c9x]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5c9x]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C9X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C9X FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4Z4:2,4-DICHLORO-5-FLUOROBENZOIC+ACID'>4Z4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Malate_synthase Malate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.9 2.3.3.9] </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=5c9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c9x OCA], [http://pdbe.org/5c9x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c9x RCSB], [http://www.ebi.ac.uk/pdbsum/5c9x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5c9x ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MASZ_MYCTU MASZ_MYCTU]] Involved in the glycolate utilization. Catalyzes the condensation and subsequent hydrolysis of acetyl-coenzyme A (acetyl-CoA) and glyoxylate to form malate and CoA (By similarity).[HAMAP-Rule:MF_00641]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Establishment or maintenance of a persistent infection by Mycobacterium tuberculosis requires the glyoxylate pathway. This is a bypass of the tricarboxylic acid cycle in which isocitrate lyase and malate synthase (GlcB) catalyze the net incorporation of carbon during growth of microorganisms on acetate or fatty acids as the primary carbon source. The glcB gene from M. tuberculosis, which encodes malate synthase, was cloned, and GlcB was expressed in Escherichia coli. The influence of media conditions on expression in M. tuberculosis indicated that this enzyme is regulated differentially to isocitrate lyase. Purified GlcB had K(m) values of 57 and 30 microm for its substrates glyoxylate and acetyl coenzyme A, respectively, and was inhibited by bromopyruvate, oxalate, and phosphoenolpyruvate. The GlcB structure was solved to 2.1-A resolution in the presence of glyoxylate and magnesium. We also report the structure of GlcB in complex with the products of the reaction, coenzyme A and malate, solved to 2.7-A resolution. Coenzyme A binds in a bent conformation, and the details of its interactions are described, together with implications on the enzyme mechanism.

-	~~Authors:~~ Huang, ~~H.-L.~~, Sacchettini, J.C.	+	Biochemical and structural studies of malate synthase from Mycobacterium tuberculosis.,Smith CV, Huang CC, Miczak A, Russell DG, Sacchettini JC, Honer zu Bentrup K J Biol Chem. 2003 Jan 17;278(3):1735-43. Epub 2002 Oct 21. PMID:12393860<ref>PMID:12393860</ref>

-	~~Description: Crystal structure of Mycobacterium tuberculosis malate synthase in complex with 2~~,4-~~dichloro~~-~~5-fluorobenzoic acid~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Sacchettini, J.C]]	+	<div class="pdbe-citations 5c9x" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Huang, H.-L~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Malate synthase]]
		+	[[Category: Huang, H L]]
		+	[[Category: Sacchettini, J C]]
		+	[[Category: Complex]]
		+	[[Category: Fragment]]
		+	[[Category: Transferase]]

OCA at 21:33, 3 August 2016

OCA — Wed, 03 Aug 2016 21:33:07 GMT

←Older revision		Revision as of 21:33, 3 August 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5c9x is ON HOLD	+	The entry 5c9x is ON HOLD until Paper Publication

	Authors: Huang, H.-L., Sacchettini, J.C.		Authors: Huang, H.-L., Sacchettini, J.C.

OCA at 09:47, 1 June 2016

OCA — Wed, 01 Jun 2016 09:47:46 GMT

←Older revision		Revision as of 09:47, 1 June 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5c9x is ON HOLD ~~until Paper Publication~~	+	The entry 5c9x is ON HOLD

	Authors: Huang, H.-L., Sacchettini, J.C.		Authors: Huang, H.-L., Sacchettini, J.C.

OCA at 01:20, 16 October 2015

OCA — Fri, 16 Oct 2015 01:20:54 GMT

←Older revision		Revision as of 01:20, 16 October 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5c9x is ON HOLD	+	The entry 5c9x is ON HOLD until Paper Publication

	Authors: Huang, H.-L., Sacchettini, J.C.		Authors: Huang, H.-L., Sacchettini, J.C.

OCA: Protected "5c9x" [edit=sysop:move=sysop]

OCA — Wed, 08 Jul 2015 13:53:25 GMT

Protected "5c9x" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:53, 8 July 2015

OCA: New page: '''Unreleased structure''' The entry 5c9x is ON HOLD Authors: Huang, H.-L., Sacchettini, J.C. Description: Crystal structure of Mycobacterium tuberculosis malate synthase in complex wi...

OCA — Wed, 08 Jul 2015 13:53:23 GMT

New page: '''Unreleased structure''' The entry 5c9x is ON HOLD Authors: Huang, H.-L., Sacchettini, J.C. Description: Crystal structure of Mycobacterium tuberculosis malate synthase in complex wi...

New page

'''Unreleased structure'''

The entry 5c9x is ON HOLD

Authors: Huang, H.-L., Sacchettini, J.C.

Description: Crystal structure of Mycobacterium tuberculosis malate synthase in complex with 2,4-dichloro-5-fluorobenzoic acid
[[Category: Unreleased Structures]]
[[Category: Sacchettini, J.C]]
[[Category: Huang, H.-L]]