3am9: Difference between revisions
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New page: '''Unreleased structure''' The entry 3am9 is ON HOLD Authors: Koji Matsumoto, Ken Okamoto, Naoki Ashizawa, Tomohiro Matsumura, Teruo Kusano, Takeshi Nishino Description: Complex of bov... |
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==Complex of bovine xanthine dehydrogenase and trihydroxy FYX-051== | |||
<StructureSection load='3am9' size='340' side='right'caption='[[3am9]], [[Resolution|resolution]] 2.17Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3am9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AM9 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]] 2.17Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=FYO:4-[5-(2,6-DIOXO-1,2,3,6-TETRAHYDROPYRIDIN-4-YL)-1H-1,2,4-TRIAZOL-3-YL]-6-OXO-1,6-DIHYDROPYRIDINE-2-CARBONITRILE'>FYO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MOS:DIOXOTHIOMOLYBDENUM(VI)+ION'>MOS</scene>, <scene name='pdbligand=MTE:PHOSPHONIC+ACIDMONO-(2-AMINO-5,6-DIMERCAPTO-4-OXO-3,7,8A,9,10,10A-HEXAHYDRO-4H-8-OXA-1,3,9,10-TETRAAZA-ANTHRACEN-7-YLMETHYL)ESTER'>MTE</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=3am9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3am9 OCA], [https://pdbe.org/3am9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3am9 RCSB], [https://www.ebi.ac.uk/pdbsum/3am9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3am9 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/XDH_BOVIN XDH_BOVIN] Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
FYX-051, 4-[5-(pyridin-4-yl)-1H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile, is a potent inhibitor of bovine milk xanthine oxidoreductase (XOR). Steady-state kinetics study showed that it initially behaved as a competitive-type inhibitor with a Ki value of 5.7x10(-9) M, then after a few minutes it formed a tight complex with XOR via a Mo-oxygen-carbon atom covalent linkage, as previously reported (Okamoto et al., 2004). Thus, FYX-051 is a hybrid-type inhibitor exhibiting both structure-based and mechanism-based inhibition. The FYX-051 XOR complex decomposed with a half-life of 20.4 hours, but the enzyme activity did not fully recover. This was found to be due to XOR-mediated conversion of FYX-051 to 2-hydroxy-FYX-051, as well as formation of di- and trihydroxy-FYX-051 during prolonged incubation for up to 72 hours. A distinct charge-transfer band was observed concomitantly with the formation of trihydroxy-FYX-051 XOR complex. Crystallographic analysis of the charge-transfer complex indicated that a Mo-nitrogen-carbon bond was formed between molybdenum of XOR and the nitrile group of trihydroxy-FYX-051. FYX-051 showed a potent and long-lasting hypouricemic effect in a rat model of potassium oxonate-induced hyperuricemia, and it seems to be a promising candidate for clinical treatment of hyperuricemia. | |||
FYX-051 : A novel and potent hybrid type inhibitor of xanthine oxidoreductase.,Matsumoto K, Okamoto K, Ashizawa N, Nishino T J Pharmacol Exp Ther. 2010 Oct 15. PMID:20952484<ref>PMID:20952484</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3am9" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Xanthine dehydrogenase 3D structures|Xanthine dehydrogenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Large Structures]] | |||
[[Category: Ashizawa N]] | |||
[[Category: Kusano T]] | |||
[[Category: Matsumoto K]] | |||
[[Category: Matsumura T]] | |||
[[Category: Nishino T]] | |||
[[Category: Okamoto K]] | |||
Latest revision as of 14:30, 1 November 2023
Complex of bovine xanthine dehydrogenase and trihydroxy FYX-051
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