3am9

From Proteopedia

(Difference between revisions)

Revision as of 12:24, 29 July 2020

Complex of bovine xanthine dehydrogenase and trihydroxy FYX-051

Structural highlights

3am9 is a 2 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , , ,
Related:	3amz, 3an1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.

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^[1]

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

References

↑ Matsumoto K, Okamoto K, Ashizawa N, Nishino T. FYX-051 : A novel and potent hybrid type inhibitor of xanthine oxidoreductase. J Pharmacol Exp Ther. 2010 Oct 15. PMID:20952484 doi:10.1124/jpet.110.174540

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/3am9"

@@ Line 1: / Line 1: @@
 ==Complex of bovine xanthine dehydrogenase and trihydroxy FYX-051==
-<StructureSection load='3am9' size='340' side='right' caption='[[3am9]], [[Resolution|resolution]] 2.17&Aring;' scene=''>
+<StructureSection load='3am9' size='340' side='right'caption='[[3am9]], [[Resolution|resolution]] 2.17&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3am9]] is a 2 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3AM9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3am9]] is a 2 chain structure with sequence from [http://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 [http://proteopedia.org/fgij/fg.htm?mol=3AM9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
+</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3amz|3amz]], [[3an1|3an1]]</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=3am9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3am9 OCA], [http://pdbe.org/3am9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3am9 RCSB], [http://www.ebi.ac.uk/pdbsum/3am9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3am9 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3am9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3am9 OCA], [http://pdbe.org/3am9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3am9 RCSB], [http://www.ebi.ac.uk/pdbsum/3am9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3am9 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 27: / Line 27: @@
 </StructureSection>
 [[Category: Bos taurus]]
+[[Category: Large Structures]]
 [[Category: Ashizawa, N]]
 [[Category: Kusano, T]]

3am9

From Proteopedia

Revision as of 12:24, 29 July 2020

Complex of bovine xanthine dehydrogenase and trihydroxy FYX-051

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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