2oat
From Proteopedia
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|SITE= <scene name='pdbsite=FMA:The+Inhibitor-Cofactor+Adduct+Has+An+Absorption+Maximum+...'>FMA</scene>, <scene name='pdbsite=FMB:The+Inhibitor-Cofactor+Adduct+Has+An+Absorption+Maximum+...'>FMB</scene> and <scene name='pdbsite=FMC:The+Inhibitor-Cofactor+Adduct+Has+An+Absorption+Maximum+...'>FMC</scene> | |SITE= <scene name='pdbsite=FMA:The+Inhibitor-Cofactor+Adduct+Has+An+Absorption+Maximum+...'>FMA</scene>, <scene name='pdbsite=FMB:The+Inhibitor-Cofactor+Adduct+Has+An+Absorption+Maximum+...'>FMB</scene> and <scene name='pdbsite=FMC:The+Inhibitor-Cofactor+Adduct+Has+An+Absorption+Maximum+...'>FMC</scene> | ||
|LIGAND= <scene name='pdbligand=PFM:1-AMINO-7-(2-METHYL-3-OXIDO-5-((PHOSPHONOXY)METHYL)-4-PYRIDOXAL-5-OXO-6-HEPTENATE'>PFM</scene> | |LIGAND= <scene name='pdbligand=PFM:1-AMINO-7-(2-METHYL-3-OXIDO-5-((PHOSPHONOXY)METHYL)-4-PYRIDOXAL-5-OXO-6-HEPTENATE'>PFM</scene> | ||
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Ornithine_aminotransferase Ornithine aminotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.13 2.6.1.13] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Ornithine_aminotransferase Ornithine aminotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.13 2.6.1.13] </span> |
|GENE= OAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= OAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oat FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oat OCA], [http://www.ebi.ac.uk/pdbsum/2oat PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2oat RCSB]</span> | ||
}} | }} | ||
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[[Category: Schirmer, T.]] | [[Category: Schirmer, T.]] | ||
[[Category: Storici, P.]] | [[Category: Storici, P.]] | ||
| - | [[Category: PFM]] | ||
[[Category: 5-fluoromethylornithine]] | [[Category: 5-fluoromethylornithine]] | ||
[[Category: aminotransferase]] | [[Category: aminotransferase]] | ||
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[[Category: pyridoxal phosphate]] | [[Category: pyridoxal phosphate]] | ||
| - | ''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 04:15:09 2008'' |
Revision as of 01:15, 31 March 2008
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| , resolution 1.95Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , and | ||||||
| Ligands: | |||||||
| Gene: | OAT (Homo sapiens) | ||||||
| Activity: | Ornithine aminotransferase, with EC number 2.6.1.13 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
ORNITHINE AMINOTRANSFERASE COMPLEXED WITH 5-FLUOROMETHYLORNITHINE
Contents |
Overview
Ornithine aminotransferase (l-ornithine:2-oxoacid delta-aminotransferase; EC 2.6.1.13), a pyridoxal-5'-phosphate-dependent mitochondrial enzyme controls the l-ornithine level in tissues by catalyzing the transfer of the delta-amino group of l-ornithine to 2-oxoglutarate, producing l-glutamate- gamma-semialdehyde and l-glutamate. (2S, 5S)-5-Fluoromethylornithine is the only inhibitor exclusively specific for ornithine aminotransferase known to date. Both in vitro and in vivo, it blocks the enzyme by a suicide reaction leading to a covalent adduct with the cofactor. The crystal structure of the enzyme-inhibitor complex was solved at a resolution of 1.95 A. No significant conformational changes compared with the native enzyme structure were observed. The structure reveals the atomic details of the cofactor-inhibitor adduct and its interactions with the active site of the enzyme. The main residues responsible for specific binding of the inhibitor are Arg180, which forms a strong salt bridge with the alpha-carboxylate and Tyr55, which is involved in a short hydrogen bond with the alpha-amino group. The experimental observation that in the racemic mixture, (2S, 5S)-5-fluoromethylornithine is exclusively responsible for the enzyme inhibition can be explained on the basis of the active site topology. Model building studies strongly suggest that the natural substrate l-ornithine, in its external aldimine adduct with the enzyme, makes use of the same recognition site as the inhibitor. It is proposed that the neutralization of the active site Arg413 by a salt bridge with Glu235 also plays an important role in productive binding of both 5-fluoromethylornithine and l-ornithine. Arg180 and Arg413 are believed to be instrumental in recognition of l-glutamate, by binding its gamma and alpha-carboxylate groups, respectively. This requires a different side-chain conformation of Glu235. Lys292 is the only obvious candidate for catalyzing the rate-limiting proton transfer steps in the transamination reaction.
Disease
Known disease associated with this structure: Gyrate atrophy of choroid and retina with ornithinemia, B6 responsive or unresponsive OMIM:[258870]
About this Structure
2OAT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of human ornithine aminotransferase complexed with the highly specific and potent inhibitor 5-fluoromethylornithine., Storici P, Capitani G, Muller R, Schirmer T, Jansonius JN, J Mol Biol. 1999 Jan 8;285(1):297-309. PMID:9878407
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