1vdv: Difference between revisions
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[[Image:1vdv.gif|left|200px]] | [[Image:1vdv.gif|left|200px]] | ||
'''Bovine Milk Xanthine Dehydrogenase Y-700 Bound Form''' | {{Structure | ||
|PDB= 1vdv |SIZE=350|CAPTION= <scene name='initialview01'>1vdv</scene>, resolution 1.98Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</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>, <scene name='pdbligand=MOS:DIOXOTHIOMOLYBDENUM(VI)+ION'>MOS</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=YSH:1-[3-CYANO-4-(NEOPENTYLOXY)PHENYL]-1H-PYRAZOLE-4-CARBOXYLIC+ACID'>YSH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> and <scene name='pdbligand=ACY:ACETIC ACID'>ACY</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Xanthine_dehydrogenase Xanthine dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.1.4 1.17.1.4] | |||
|GENE= | |||
}} | |||
'''Bovine Milk Xanthine Dehydrogenase Y-700 Bound Form''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1VDV is a [ | 1VDV is a [[Single protein]] structure of 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=1VDV OCA]. | ||
==Reference== | ==Reference== | ||
Y-700 [1-[3-Cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid]: a potent xanthine oxidoreductase inhibitor with hepatic excretion., Fukunari A, Okamoto K, Nishino T, Eger BT, Pai EF, Kamezawa M, Yamada I, Kato N, J Pharmacol Exp Ther. 2004 Nov;311(2):519-28. Epub 2004 Jun 9. PMID:[http:// | Y-700 [1-[3-Cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid]: a potent xanthine oxidoreductase inhibitor with hepatic excretion., Fukunari A, Okamoto K, Nishino T, Eger BT, Pai EF, Kamezawa M, Yamada I, Kato N, J Pharmacol Exp Ther. 2004 Nov;311(2):519-28. Epub 2004 Jun 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15190124 15190124] | ||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: y-700]] | [[Category: y-700]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:44:15 2008'' | ||
Revision as of 15:44, 20 March 2008
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| , resolution 1.98Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , , , and | ||||||
| Activity: | Xanthine dehydrogenase, with EC number 1.17.1.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Bovine Milk Xanthine Dehydrogenase Y-700 Bound Form
OverviewOverview
Y-700 (1-[3-Cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid) is a newly synthesized inhibitor of xanthine oxidoreductase (XOR). Steady-state kinetics with the bovine milk enzyme indicated a mixed type inhibition with K(i) and K(i) ' values of 0.6 and 3.2 nM, respectively. Titration experiments showed that Y-700 bound tightly both to the active sulfo-form and to the inactive desulfo-form of the enzyme with K(d) values of 0.9 and 2.8 nM, respectively. X-ray crystallographic analysis of the enzyme-inhibitor complex revealed that Y-700 closely interacts with the channel leading to the molybdenum-pterin active site but does not directly coordinate to the molybdenum ion. In oxonate-treated rats, orally administered Y-700 (1-10 mg/kg) dose dependently lowered plasma urate levels. At a dose of 10 mg/kg, the hypouricemic action of Y-700 was more potent and of longer duration than that of 4-hydroxypyrazolo(3,4-d)pyrimidine, whereas its action was approximately equivalent to that of 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid, a nonpurine inhibitor of XOR. In normal rats, orally administered Y-700 (0.3-3 mg/kg) dose dependently reduced the urinary excretion of urate and allantoin, accompanied by an increase in the excretion of hypoxanthine and xanthine. Y-700 (1 mg/kg) was absorbed rapidly by the oral route with high bioavailability (84.1%). Y-700 was hardly excreted via the kidneys but was mainly cleared via the liver. These results suggest that Y-700 will be a promising candidate for the treatment of hyperuricemia and other diseases in which XOR may be involved.
About this StructureAbout this Structure
1VDV is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
ReferenceReference
Y-700 [1-[3-Cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid]: a potent xanthine oxidoreductase inhibitor with hepatic excretion., Fukunari A, Okamoto K, Nishino T, Eger BT, Pai EF, Kamezawa M, Yamada I, Kato N, J Pharmacol Exp Ther. 2004 Nov;311(2):519-28. Epub 2004 Jun 9. PMID:15190124
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