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2o4h
From Proteopedia
| 2o4h, resolution 2.70Å () | |||||||||
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| Sites: | , , and | ||||||||
| Ligands: | , | ||||||||
| Gene: | ASPA, ACY2, ASP (Homo sapiens) | ||||||||
| Activity: | Aspartoacylase, with EC number 3.5.1.15 | ||||||||
| Domains: | PRK02259 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Human brain aspartoacylase complex with intermediate analog (N-phosphonomethyl-L-aspartate)
Canavan disease is a fatal neurological disorder caused by the malfunctioning of a single metabolic enzyme, aspartoacylase, that catalyzes the deacetylation of N-acetyl- l-aspartate to produce l-aspartate and acetate. The structure of human brain aspartoacylase has been determined in complex with a stable tetrahedral intermediate analogue, N-phosphonomethyl- l-aspartate. This potent inhibitor forms multiple interactions between each of its heteroatoms and the substrate binding groups arrayed within the active site. The binding of the catalytic intermediate analogue induces the conformational ordering of several substrate binding groups, thereby setting up the active site for catalysis. The highly ordered binding of this inhibitor has allowed assignments to be made for substrate binding groups and provides strong support for a carboxypeptidase-type mechanism for the hydrolysis of the amide bond of the substrate, N-acetyl- l-aspartate.
Examination of the Mechanism of Human Brain Aspartoacylase through the Binding of an Intermediate Analogue(,)., Le Coq J, Pavlovsky A, Malik R, Sanishvili R, Xu C, Viola RE, Biochemistry. 2008 Mar 18;47(11):3484-92. Epub 2008 Feb 23. PMID:18293939
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2O4H is a 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Le Coq J, Pavlovsky A, Malik R, Sanishvili R, Xu C, Viola RE. Examination of the Mechanism of Human Brain Aspartoacylase through the Binding of an Intermediate Analogue(,). Biochemistry. 2008 Mar 18;47(11):3484-92. Epub 2008 Feb 23. PMID:18293939 doi:10.1021/bi702400x
Page seeded by OCA on Wed Feb 18 10:02:41 2009

