2o4h
From Proteopedia
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{{Structure | {{Structure | ||
|PDB= 2o4h |SIZE=350|CAPTION= <scene name='initialview01'>2o4h</scene>, resolution 2.70Å | |PDB= 2o4h |SIZE=350|CAPTION= <scene name='initialview01'>2o4h</scene>, resolution 2.70Å | ||
| - | |SITE= | + | |SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Residue+A+401'>AC1</scene>, <scene name='pdbsite=AC2:Zn+Binding+Site+For+Residue+B+401'>AC2</scene>, <scene name='pdbsite=AC3:As9+Binding+Site+For+Residue+A+501'>AC3</scene> and <scene name='pdbsite=AC4:As9+Binding+Site+For+Residue+B+501'>AC4</scene> |
| - | + | |LIGAND= <scene name='pdbligand=AS9:N-[HYDROXY(METHYL)PHOSPHORYL]-L-ASPARTIC+ACID'>AS9</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Aspartoacylase Aspartoacylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.15 3.5.1.15] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Aspartoacylase Aspartoacylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.15 3.5.1.15] </span> |
|GENE= ASPA, ACY2, ASP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= ASPA, ACY2, ASP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=PRK02259 PRK02259]</span> | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2o4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o4h OCA], [http://www.ebi.ac.uk/pdbsum/2o4h PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=2o4h RCSB]</span> | ||
}} | }} | ||
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| - | == | + | ==Overview== |
| - | + | 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. | |
==About this Structure== | ==About this Structure== | ||
2O4H is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O4H OCA]. | 2O4H is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O4H OCA]. | ||
| + | |||
| + | ==Reference== | ||
| + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/18293939 18293939] | ||
[[Category: Aspartoacylase]] | [[Category: Aspartoacylase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: Sanishvili, R.]] | [[Category: Sanishvili, R.]] | ||
[[Category: Viola, R E.]] | [[Category: Viola, R E.]] | ||
| - | [[Category: AS9]] | ||
| - | [[Category: ZN]] | ||
[[Category: acy2]] | [[Category: acy2]] | ||
[[Category: aminoacylase-2]] | [[Category: aminoacylase-2]] | ||
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[[Category: zinc-dependent hydrolase]] | [[Category: zinc-dependent hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 26 10:02:06 2008'' |
Revision as of 08:02, 26 March 2008
| |||||||
| , resolution 2.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , and | ||||||
| Ligands: | , | ||||||
| Gene: | ASPA, ACY2, ASP (Homo sapiens) | ||||||
| Activity: | Aspartoacylase, with EC number 3.5.1.15 | ||||||
| Domains: | PRK02259 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, JenaLib, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human brain aspartoacylase complex with intermediate analog (N-phosphonomethyl-L-aspartate)
Overview
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.
About this Structure
2O4H is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Wed Mar 26 10:02:06 2008
