2O53

Crystal structure of apo-Aspartoacylase from human brain

Summary for 2O53

• Entry DOI: 10.2210/pdb2o53/pdb
• Related: 2O4H
• Descriptor: Aspartoacylase, ZINC ION, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: canavan disease, n-acetyl-l-aspartate, zinc-dependent hydrolase, aspartoacylase family, aminoacylase-2, acy2, aspa, n-phosphonomethyl-l-aspartate, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P45381
• Total number of polymer chains: 2
• Total formula weight: 72078.87

Authors

Le Coq, J.,Pavlovsky, A.,Sanishvili, R.,Viola, R.E. (deposition date: 2006-12-05, release date: 2007-11-06, Last modification date: 2023-08-30)

Primary citation

Le Coq, J.,Pavlovsky, A.,Malik, R.,Sanishvili, R.,Xu, C.,Viola, R.E.
Examination of the Mechanism of Human Brain Aspartoacylase through the Binding of an Intermediate Analogue.
Biochemistry, 47:3484-3492, 2008

PubMed Abstract: 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.

PubMed: 18293939
DOI: 10.1021/bi702400x

Experimental method

X-RAY DIFFRACTION (2.7 Å)