2e48
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(New page: 200px<br /> <applet load="2e48" size="450" color="white" frame="true" align="right" spinBox="true" caption="2e48, resolution 2.90Å" /> '''Crystal Structure o...)
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Revision as of 19:38, 12 November 2007
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Crystal Structure of Human D-Amino Acid Oxidase: Substrate-Free Holoenzyme
Contents |
Overview
d-Amino acid oxidase (DAO) degrades the gliotransmitter d-serine, a potent, endogenous ligand of N-methyl-d-aspartate type glutamate receptors. It, also has been suggested that d-DOPA, the stereoisomer of l-DOPA, is, oxidized by DAO and then converted to dopamine via an alternative, biosynthetic pathway. Here, we provide direct crystallographic evidence, that d-DOPA is readily fitted into the active site of human DAO, where it, is oxidized by the enzyme. Moreover, our kinetic data show that the, maximal velocity for oxidation of d-DOPA is much greater than for, d-serine, which strongly supports the proposed alternative pathway for, dopamine biosynthesis in the treatment of Parkinson's disease. In, addition, determination of the structures of human DAO in various states, revealed that the conformation of the hydrophobic VAAGL stretch (residues, 47-51) to be uniquely stable in the human enzyme, which provides a, structural basis for the unique kinetic features of human DAO.
Disease
Known diseases associated with this structure: Schizophrenia OMIM:[124050]
About this Structure
2E48 is a Single protein structure of sequence from Homo sapiens with FAD as ligand. Active as D-amino-acid oxidase, with EC number 1.4.3.3 Full crystallographic information is available from OCA.
Reference
Structural basis of d-DOPA oxidation by d-amino acid oxidase: Alternative pathway for dopamine biosynthesis., Kawazoe T, Tsuge H, Imagawa T, Aki K, Kuramitsu S, Fukui K, Biochem Biophys Res Commun. 2007 Apr 6;355(2):385-91. Epub 2007 Feb 8. PMID:17303072
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