2e48
From Proteopedia
(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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| - | [[Image:2e48.gif|left|200px]]<br /> | + | [[Image:2e48.gif|left|200px]]<br /><applet load="2e48" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2e48" size=" | + | |
caption="2e48, resolution 2.90Å" /> | caption="2e48, resolution 2.90Å" /> | ||
'''Crystal Structure of Human D-Amino Acid Oxidase: Substrate-Free Holoenzyme'''<br /> | '''Crystal Structure of Human D-Amino Acid Oxidase: Substrate-Free Holoenzyme'''<br /> | ||
==Overview== | ==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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2E48 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FAD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/D-amino-acid_oxidase D-amino-acid oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.3 1.4.3.3] Full crystallographic information is available from [http:// | + | 2E48 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/D-amino-acid_oxidase D-amino-acid oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.3 1.4.3.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E48 OCA]. |
==Reference== | ==Reference== | ||
| - | Structural basis of | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17303072 17303072] |
[[Category: D-amino-acid oxidase]] | [[Category: D-amino-acid oxidase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: substrate-free holoenzyme]] | [[Category: substrate-free holoenzyme]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:05:50 2008'' |
Revision as of 15:05, 21 February 2008
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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 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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