5wqj

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of 3-Mercaptopyruvate Sulfurtransferase(3MST) in complex with compound1

Structural highlights

5wqj is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.2Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

THTM_MOUSE Transfer of a sulfur ion to cyanide or to other thiol compounds. Also has weak rhodanese activity. Detoxifies cyanide and is required for thiosulfate biosynthesis. Acts as an antioxidant. In combination with cysteine aminotransferase (CAT), contributes to the catabolism of cysteine and is an important producer of hydrogen sulfide in the brain, retina and vascular endothelial cells. Hydrogen sulfide H(2)S is an important synaptic modulator, signaling molecule, smooth muscle contractor and neuroprotectant. Its production by the 3MST/CAT pathway is regulated by calcium ions.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Very recent studies indicate that sulfur atoms with oxidation state 0 or -1, called sulfane sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a persulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the persulfur anion of the persulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.

Discovery and Mechanistic Characterization of Selective Inhibitors of H2S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide.,Hanaoka K, Sasakura K, Suwanai Y, Toma-Fukai S, Shimamoto K, Takano Y, Shibuya N, Terai T, Komatsu T, Ueno T, Ogasawara Y, Tsuchiya Y, Watanabe Y, Kimura H, Wang C, Uchiyama M, Kojima H, Okabe T, Urano Y, Shimizu T, Nagano T Sci Rep. 2017 Jan 12;7:40227. doi: 10.1038/srep40227. PMID:28079151^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shibuya N, Tanaka M, Yoshida M, Ogasawara Y, Togawa T, Ishii K, Kimura H. 3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain. Antioxid Redox Signal. 2009 Apr;11(4):703-14. PMID:18855522 doi:10.1089/ars.2008.2253
↑ Mikami Y, Shibuya N, Kimura Y, Nagahara N, Yamada M, Kimura H. Hydrogen sulfide protects the retina from light-induced degeneration by the modulation of Ca2+ influx. J Biol Chem. 2011 Nov 11;286(45):39379-86. PMID:21937432 doi:10.1074/jbc.M111.298208
↑ Mikami Y, Kimura H. A mechanism of retinal protection from light-induced degeneration by hydrogen sulfide. Commun Integr Biol. 2012 Mar 1;5(2):169-71. PMID:22808324 doi:10.4161/cib.18679
↑ Hanaoka K, Sasakura K, Suwanai Y, Toma-Fukai S, Shimamoto K, Takano Y, Shibuya N, Terai T, Komatsu T, Ueno T, Ogasawara Y, Tsuchiya Y, Watanabe Y, Kimura H, Wang C, Uchiyama M, Kojima H, Okabe T, Urano Y, Shimizu T, Nagano T. Discovery and Mechanistic Characterization of Selective Inhibitors of H2S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide. Sci Rep. 2017 Jan 12;7:40227. doi: 10.1038/srep40227. PMID:28079151 doi:http://dx.doi.org/10.1038/srep40227
↑ Hanaoka K, Sasakura K, Suwanai Y, Toma-Fukai S, Shimamoto K, Takano Y, Shibuya N, Terai T, Komatsu T, Ueno T, Ogasawara Y, Tsuchiya Y, Watanabe Y, Kimura H, Wang C, Uchiyama M, Kojima H, Okabe T, Urano Y, Shimizu T, Nagano T. Discovery and Mechanistic Characterization of Selective Inhibitors of H2S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide. Sci Rep. 2017 Jan 12;7:40227. doi: 10.1038/srep40227. PMID:28079151 doi:http://dx.doi.org/10.1038/srep40227

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5wqj"

Categories: Large Structures | Mus musculus | Shimizu T | Suwanai Y | Toma-Fukai S

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5wqj is ON HOLD
+==Crystal structure of 3-Mercaptopyruvate Sulfurtransferase(3MST) in complex with compound1==
+<StructureSection load='5wqj' size='340' side='right'caption='[[5wqj]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5wqj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WQJ FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7N3:2-[2-[(4-oxidanylidene-3~{H}-quinazolin-2-yl)sulfanyl]ethanoylamino]thiophene-3-carboxamide'>7N3</scene>, <scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5wqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wqj OCA], [https://pdbe.org/5wqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wqj RCSB], [https://www.ebi.ac.uk/pdbsum/5wqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wqj ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/THTM_MOUSE THTM_MOUSE] Transfer of a sulfur ion to cyanide or to other thiol compounds. Also has weak rhodanese activity. Detoxifies cyanide and is required for thiosulfate biosynthesis. Acts as an antioxidant. In combination with cysteine aminotransferase (CAT), contributes to the catabolism of cysteine and is an important producer of hydrogen sulfide in the brain, retina and vascular endothelial cells. Hydrogen sulfide H(2)S is an important synaptic modulator, signaling molecule, smooth muscle contractor and neuroprotectant. Its production by the 3MST/CAT pathway is regulated by calcium ions.<ref>PMID:18855522</ref> <ref>PMID:21937432</ref> <ref>PMID:22808324</ref> <ref>PMID:28079151</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Very recent studies indicate that sulfur atoms with oxidation state 0 or -1, called sulfane sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a persulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the persulfur anion of the persulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.
-Authors:
+Discovery and Mechanistic Characterization of Selective Inhibitors of H2S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide.,Hanaoka K, Sasakura K, Suwanai Y, Toma-Fukai S, Shimamoto K, Takano Y, Shibuya N, Terai T, Komatsu T, Ueno T, Ogasawara Y, Tsuchiya Y, Watanabe Y, Kimura H, Wang C, Uchiyama M, Kojima H, Okabe T, Urano Y, Shimizu T, Nagano T Sci Rep. 2017 Jan 12;7:40227. doi: 10.1038/srep40227. PMID:28079151<ref>PMID:28079151</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5wqj" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Sulfurtransferase|Sulfurtransferase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Shimizu T]]
+[[Category: Suwanai Y]]
+[[Category: Toma-Fukai S]]

5wqj

From Proteopedia

Current revision

Crystal structure of 3-Mercaptopyruvate Sulfurtransferase(3MST) in complex with compound1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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