2e4a: Difference between revisions
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|PDB= 2e4a |SIZE=350|CAPTION= <scene name='initialview01'>2e4a</scene>, resolution 2.60Å | |PDB= 2e4a |SIZE=350|CAPTION= <scene name='initialview01'>2e4a</scene>, resolution 2.60Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=BE2:2-AMINOBENZOIC+ACID'>BE2</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene> | ||
|ACTIVITY= [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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2du8|2DU8]], [[2e48|2E48]], [[2e49|2E49]], [[2e82|2E82]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e4a OCA], [http://www.ebi.ac.uk/pdbsum/2e4a PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2e4a RCSB]</span> | |||
}} | }} | ||
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==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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Kawazoe, T.]] | [[Category: Kawazoe, T.]] | ||
[[Category: Tsuge, H.]] | [[Category: Tsuge, H.]] | ||
[[Category: o-aminobenzoate complex]] | [[Category: o-aminobenzoate complex]] | ||
[[Category: structurally ambivalent peptide]] | [[Category: structurally ambivalent peptide]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:43:32 2008'' | ||
Revision as of 02:43, 31 March 2008
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| , resolution 2.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | D-amino-acid oxidase, with EC number 1.4.3.3 | ||||||
| Related: | 2DU8, 2E48, 2E49, 2E82
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Human D-Amino Acid Oxidase in complex with o-aminobenzoate
OverviewOverview
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.
About this StructureAbout this Structure
2E4A is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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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