8biu - Revision history

OCA at 08:18, 7 February 2024

OCA — Wed, 07 Feb 2024 08:18:38 GMT

←Older revision		Revision as of 08:18, 7 February 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/B6K8Y1_TOXGV B6K8Y1_TOXGV]		[https://www.uniprot.org/uniprot/B6K8Y1_TOXGV B6K8Y1_TOXGV]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Cystathionine gamma-lyase (CGL) is a PLP-dependent enzyme that catalyzes the last step of the reverse transsulfuration route for endogenous cysteine biosynthesis. The canonical CGL-catalyzed process consists of an alpha,gamma-elimination reaction that breaks down cystathionine into cysteine, alpha-ketobutyrate, and ammonia. In some species, the enzyme can alternatively use cysteine as a substrate, resulting in the production of hydrogen sulfide (H(2) S). Importantly, inhibition of the enzyme and consequently of its H(2) S production activity, makes multiresistant bacteria considerably more susceptible to antibiotics. Other organisms, such as Toxoplasma gondii, the causative agent of toxoplasmosis, encode a CGL enzyme (TgCGL) that almost exclusively catalyzes the canonical process, with only minor reactivity to cysteine. Interestingly, the substitution of N360 by a serine (the equivalent amino acid residue in the human enzyme) at the active site changes the specificity of TgCGL for the catalysis of cystathionine, resulting in an enzyme that can cleave both the CgammaS and the CbetaS bond of cystathionine. Based on these findings and to deepen the molecular basis underlying the enzyme-substrate specificity, we have elucidated the crystal structures of native TgCGL and the variant TgCGL-N360S from crystals grown in the presence of cystathionine, cysteine, and the inhibitor d,l-propargylglycine (PPG). Our structures reveal the binding mode of each molecule within the catalytic cavity and help explain the inhibitory behavior of cysteine and PPG. A specific inhibitory mechanism of TgCGL by PPG is proposed.
-
-	Structural basis of the inhibition of cystathionine gamma-lyase from Toxoplasma gondii by propargylglycine and cysteine.,Fernandez-Rodriguez C, Conter C, Oyenarte I, Favretto F, Quintana I, Martinez-Chantar ML, Astegno A, Martinez-Cruz LA Protein Sci. 2023 Apr;32(4):e4619. doi: 10.1002/pro.4619. PMID:36883335<ref>PMID:36883335</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 8biu" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 11:26, 15 November 2023

OCA — Wed, 15 Nov 2023 11:26:59 GMT

←Older revision		Revision as of 11:26, 15 November 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8biu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BIU FirstGlance]. <br>		<table><tr><td colspan='2'>[[8biu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BIU FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2KT:2-KETOBUTYRIC+ACID'>2KT</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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]] 1.899Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2KT:2-KETOBUTYRIC+ACID'>2KT</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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=8biu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8biu OCA], [https://pdbe.org/8biu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8biu RCSB], [https://www.ebi.ac.uk/pdbsum/8biu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8biu 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=8biu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8biu OCA], [https://pdbe.org/8biu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8biu RCSB], [https://www.ebi.ac.uk/pdbsum/8biu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8biu ProSAT]</span></td></tr>
	</table>		</table>

OCA at 20:30, 12 April 2023

OCA — Wed, 12 Apr 2023 20:30:16 GMT

←Older revision		Revision as of 20:30, 12 April 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8biu is ~~ON HOLD until Paper~~ Publication	+	==Cystathionine gamma-lyase in complex with cystathionine==
		+	<StructureSection load='8biu' size='340' side='right'caption='[[8biu]], [[Resolution\|resolution]] 1.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8biu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BIU FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2KT:2-KETOBUTYRIC+ACID'>2KT</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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=8biu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8biu OCA], [https://pdbe.org/8biu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8biu RCSB], [https://www.ebi.ac.uk/pdbsum/8biu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8biu ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/B6K8Y1_TOXGV B6K8Y1_TOXGV]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cystathionine gamma-lyase (CGL) is a PLP-dependent enzyme that catalyzes the last step of the reverse transsulfuration route for endogenous cysteine biosynthesis. The canonical CGL-catalyzed process consists of an alpha,gamma-elimination reaction that breaks down cystathionine into cysteine, alpha-ketobutyrate, and ammonia. In some species, the enzyme can alternatively use cysteine as a substrate, resulting in the production of hydrogen sulfide (H(2) S). Importantly, inhibition of the enzyme and consequently of its H(2) S production activity, makes multiresistant bacteria considerably more susceptible to antibiotics. Other organisms, such as Toxoplasma gondii, the causative agent of toxoplasmosis, encode a CGL enzyme (TgCGL) that almost exclusively catalyzes the canonical process, with only minor reactivity to cysteine. Interestingly, the substitution of N360 by a serine (the equivalent amino acid residue in the human enzyme) at the active site changes the specificity of TgCGL for the catalysis of cystathionine, resulting in an enzyme that can cleave both the CgammaS and the CbetaS bond of cystathionine. Based on these findings and to deepen the molecular basis underlying the enzyme-substrate specificity, we have elucidated the crystal structures of native TgCGL and the variant TgCGL-N360S from crystals grown in the presence of cystathionine, cysteine, and the inhibitor d,l-propargylglycine (PPG). Our structures reveal the binding mode of each molecule within the catalytic cavity and help explain the inhibitory behavior of cysteine and PPG. A specific inhibitory mechanism of TgCGL by PPG is proposed.

-	~~Authors:~~ Fernandez-Rodriguez, C., Conter, C., Oyenarte, I., Favretto, F., Quintana, I., Martinez-Chantar~~, M.L.~~, Astegno, A., Martinez-Cruz~~, L~~.A.	+	Structural basis of the inhibition of cystathionine gamma-lyase from Toxoplasma gondii by propargylglycine and cysteine.,Fernandez-Rodriguez C, Conter C, Oyenarte I, Favretto F, Quintana I, Martinez-Chantar ML, Astegno A, Martinez-Cruz LA Protein Sci. 2023 Apr;32(4):e4619. doi: 10.1002/pro.4619. PMID:36883335<ref>PMID:36883335</ref>

-	~~Description: Cystathionine gamma~~-~~lyase in complex with cystathionine~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Favretto, F~~]]	+	<div class="pdbe-citations 8biu" style="background-color:#fffaf0;"></div>
-	[[Category: Astegno, A]]	+	== References ==
-	[[Category: ~~Martinez-Cruz, L.A~~]]	+	<references/>
-	[[Category: ~~Oyenarte, I~~]]	+	__TOC__
-	[[Category: Martinez-Chantar~~, M.L~~]]	+	</StructureSection>
-	[[Category: ~~Fernandez~~-~~Rodriguez, C~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Conter, C~~]]	+	[[Category: Toxoplasma gondii]]
-	[[Category: Quintana, I]]	+	[[Category: Astegno A]]
		+	[[Category: Conter C]]
		+	[[Category: Favretto F]]
		+	[[Category: Fernandez-Rodriguez C]]
		+	[[Category: Martinez-Chantar ML]]
		+	[[Category: Martinez-Cruz LA]]
		+	[[Category: Oyenarte I]]
		+	[[Category: Quintana I]]

OCA at 05:56, 21 December 2022

OCA — Wed, 21 Dec 2022 05:56:11 GMT

←Older revision		Revision as of 05:56, 21 December 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8biu is ON HOLD	+	The entry 8biu is ON HOLD until Paper Publication

-	Authors:	+	Authors: Fernandez-Rodriguez, C., Conter, C., Oyenarte, I., Favretto, F., Quintana, I., Martinez-Chantar, M.L., Astegno, A., Martinez-Cruz, L.A.

-	Description:	+	Description: Cystathionine gamma-lyase in complex with cystathionine
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Favretto, F]]
		+	[[Category: Astegno, A]]
		+	[[Category: Martinez-Cruz, L.A]]
		+	[[Category: Oyenarte, I]]
		+	[[Category: Martinez-Chantar, M.L]]
		+	[[Category: Fernandez-Rodriguez, C]]
		+	[[Category: Conter, C]]
		+	[[Category: Quintana, I]]

OCA: Protected "8biu" [edit=sysop:move=sysop]

OCA — Wed, 09 Nov 2022 04:56:59 GMT

Protected "8biu" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:56, 9 November 2022

OCA: New page: '''Unreleased structure''' The entry 8biu is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 09 Nov 2022 04:56:58 GMT

New page: '''Unreleased structure''' The entry 8biu is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8biu is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]