6nba - Revision history

OCA at 06:48, 11 October 2023

2023-10-11T06:48:49Z

←Older revision		Revision as of 06:48, 11 October 2023
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	<StructureSection load='6nba' size='340' side='right'caption='[[6nba]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='6nba' size='340' side='right'caption='[[6nba]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nba]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NBA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NBA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nba]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NBA FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=P1T:2~~-[~~({3-HYDROXY-2-METHYL-5-~~[~~(PHOSPHONOOXY)METHYL~~]~~PYRIDIN-4-YL}METHYL)AMINO~~]~~ACRYLIC+ACID'>P1T</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]] 2.495Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>CTH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P1T:2-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]ACRYLIC+ACID'>P1T</scene></td></tr>
-	~~<tr id='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Cystathionine_gamma~~-~~lyase Cystathionine gamma~~-~~lyase~~]~~, with EC number [http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=~~4~~.4.1.1 4.4.1.1~~] </~~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=6nba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nba OCA], [https://pdbe.org/6nba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nba RCSB], [https://www.ebi.ac.uk/pdbsum/6nba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nba 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=6nba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nba OCA], [~~http~~://pdbe.org/6nba PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6nba RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6nba PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6nba ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN]] Defects in CTH are the cause of cystathioninuria (CSTNU) [MIM:[~~http~~://omim.org/entry/219500 219500]]. It is an autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion.<ref>PMID:18476726</ref> <ref>PMID:12574942</ref>	+	[https://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN] Defects in CTH are the cause of cystathioninuria (CSTNU) [MIM:[https://omim.org/entry/219500 219500]. It is an autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion.<ref>PMID:18476726</ref> <ref>PMID:12574942</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN]] Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.<ref>PMID:19261609</ref> <ref>PMID:22169477</ref> <ref>PMID:19019829</ref>	+	[https://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN] Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.<ref>PMID:19261609</ref> <ref>PMID:22169477</ref> <ref>PMID:19019829</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Cystathionine gamma-lyase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Banerjee, R]]	+	[[Category: Banerjee R]]
-	[[Category: Cho, U S]]	+	[[Category: Cho U-S]]
-	[[Category: Kim, H]]	+	[[Category: Kim H]]
-	[[Category: Yadav~~, P K]]~~	+	[[Category: Yadav PK]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Lyase~~]]	+

OCA at 08:39, 24 July 2019

2019-07-24T08:39:26Z

←Older revision		Revision as of 08:39, 24 July 2019
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	<StructureSection load='6nba' size='340' side='right'caption='[[6nba]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='6nba' size='340' side='right'caption='[[6nba]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nba]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NBA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NBA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nba]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NBA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NBA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P1T:2-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]ACRYLIC+ACID'>P1T</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P1T:2-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]ACRYLIC+ACID'>P1T</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CTH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cystathionine_gamma-lyase Cystathionine gamma-lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.1 4.4.1.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cystathionine_gamma-lyase Cystathionine gamma-lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.1 4.4.1.1] </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=6nba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nba OCA], [http://pdbe.org/6nba PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nba RCSB], [http://www.ebi.ac.uk/pdbsum/6nba PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nba 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=6nba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nba OCA], [http://pdbe.org/6nba PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nba RCSB], [http://www.ebi.ac.uk/pdbsum/6nba PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nba ProSAT]</span></td></tr>
Line 26:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Cystathionine gamma-lyase]]		[[Category: Cystathionine gamma-lyase]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Banerjee, R]]		[[Category: Banerjee, R]]

OCA at 06:32, 19 June 2019

2019-06-19T06:32:41Z

←Older revision		Revision as of 06:32, 19 June 2019
Line 12:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN]] Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.<ref>PMID:19261609</ref> <ref>PMID:22169477</ref> <ref>PMID:19019829</ref>		[[http://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN]] Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.<ref>PMID:19261609</ref> <ref>PMID:22169477</ref> <ref>PMID:19019829</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Hydrogen sulfide (H2S) is a gaseous signaling molecule, which modulates a wide range of mammalian physiological processes. Cystathionine gamma-lyase (CSE) catalyzes H2S synthesis and is a potential target for modulating H2S levels under pathophysiological conditions. CSE is inhibited by propargylglycine (PPG), a widely used mechanism-based inhibitor. In this study, we report that inhibition of H2S synthesis from cysteine but not the canonical cystathionine cleavage reaction catalyzed by CSE in vitro, is sensitive to pre-incubation of the enzyme with PPG. In contrast, the efficacy of S-3-carboxpropyl-L-cysteine (CPC) a new inhibitor described herein, was not dependent on the order of substrate/inhibitor addition. We observed that CPC inhibited the gamma-elimination reaction of cystathionine and H2S synthesis from cysteine by human CSE with Ki values of 50 +/- 3 microM and 180 +/- 15 microM, respectively. We noted that CPC spared the other enzymes involved either directly (cystathionine beta-synthase, mercaptopyruvate sulfurtransferase) or indirectly (cysteine aminotransferase) in H2S biogenesis. CPC also targeted CSE in cultured cells inhibiting transsulfuration flux by 80-90% as monitored by the transfer of radiolabel from [35S]-methionine to glutathione. The 2.5A resolution crystal structure of human CSE in complex with the CPC-derived aminoacrylate intermediate, provided a structural framework for the molecular basis of its inhibitory effect. In summary, our study reveals a previously unknown confounding effect of PPG, widely used to inhibit CSE-dependent H2S synthesis, and reports on an alternative inhibitor, CPC, which could be used as a scaffold to develop more potent H2S biogenesis inhibitors.
		+
		+	S-3-Carboxypropyl-L-cysteine specifically inhibits cystathionine gamma-lyase-dependent hydrogen sulfide synthesis.,Yadav PK, Vitvitsky V, Kim H, White A, Cho US, Banerjee R J Biol Chem. 2019 Jun 3. pii: RA119.009047. doi: 10.1074/jbc.RA119.009047. PMID:31160338<ref>PMID:31160338</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6nba" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 05:40, 12 June 2019

2019-06-12T05:40:08Z

←Older revision		Revision as of 05:40, 12 June 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6nba is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of Human Cystathionine gamma lyase with S-3-Carboxpropyl-L-Cysteine==
-		+	<StructureSection load='6nba' size='340' side='right'caption='[[6nba]], [[Resolution\|resolution]] 2.50Å' scene=''>
-	~~Authors~~: ~~Kim~~, H., ~~Yadav, P~~.K., ~~Banerjee~~, R., ~~Cho~~, U.-S.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6nba]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NBA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NBA FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure~~ of ~~Human Cystathionine gamma lyase with S~~-3-~~Carboxpropyl~~-L-~~Cysteine~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P1T:2-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]ACRYLIC+ACID'>P1T</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/Cystathionine_gamma-lyase Cystathionine gamma-lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.1 4.4.1.1] </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=6nba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nba OCA], [http://pdbe.org/6nba PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nba RCSB], [http://www.ebi.ac.uk/pdbsum/6nba PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nba ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN]] Defects in CTH are the cause of cystathioninuria (CSTNU) [MIM:[http://omim.org/entry/219500 219500]]. It is an autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion.<ref>PMID:18476726</ref> <ref>PMID:12574942</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN]] Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.<ref>PMID:19261609</ref> <ref>PMID:22169477</ref> <ref>PMID:19019829</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Cystathionine gamma-lyase]]
		+	[[Category: Large Structures]]
		+	[[Category: Banerjee, R]]
		+	[[Category: Cho, U S]]
	[[Category: Kim, H]]		[[Category: Kim, H]]
-	[[Category: ~~Banerjee~~, R]]	+	[[Category: Yadav, P K]]
-	[[Category: ~~Cho, U.-S~~]]	+	[[Category: Complex]]
-	[[Category: ~~Yadav, P.K~~]]	+	[[Category: Lyase]]

OCA at 06:33, 19 December 2018

2018-12-19T06:33:56Z

←Older revision		Revision as of 06:33, 19 December 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Kim, H., Yadav, P.K., Banerjee, R., Cho, U.-S.		Authors: Kim, H., Yadav, P.K., Banerjee, R., Cho, U.-S.

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

2018-12-12T05:27:46Z

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

←Older revision

Revision as of 05:27, 12 December 2018

OCA: New page: '''Unreleased structure''' The entry 6nba is ON HOLD Authors: Kim, H., Yadav, P.K., Banerjee, R., Cho, U.-S. Description: Crystal structure of Human Cystathionine gamma lyase with S-3-...

2018-12-12T05:27:45Z

New page: '''Unreleased structure''' The entry 6nba is ON HOLD Authors: Kim, H., Yadav, P.K., Banerjee, R., Cho, U.-S. Description: Crystal structure of Human Cystathionine gamma lyase with S-3-...

New page

'''Unreleased structure'''

The entry 6nba is ON HOLD

Authors: Kim, H., Yadav, P.K., Banerjee, R., Cho, U.-S.

Description: Crystal structure of Human Cystathionine gamma lyase with S-3-Carboxpropyl-L-Cysteine
[[Category: Unreleased Structures]]
[[Category: Kim, H]]
[[Category: Banerjee, R]]
[[Category: Cho, U.-S]]
[[Category: Yadav, P.K]]