2byl
From Proteopedia
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'''STRUCTURE OF ORNITHINE AMINOTRANSFERASE TRIPLE MUTANT Y85I Y55A G320F''' | '''STRUCTURE OF ORNITHINE AMINOTRANSFERASE TRIPLE MUTANT Y85I Y55A G320F''' | ||
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[[Category: Peneff, C.]] | [[Category: Peneff, C.]] | ||
[[Category: Schirmer, T.]] | [[Category: Schirmer, T.]] | ||
| - | [[Category: | + | [[Category: Aminotransferase]] |
| - | [[Category: | + | [[Category: Disease mutation]] |
| - | [[Category: | + | [[Category: Mitochondrion]] |
| - | [[Category: | + | [[Category: Plp-dependent enzyme]] |
| - | [[Category: | + | [[Category: Polymorphism]] |
| - | [[Category: | + | [[Category: Pyridoxal phosphate]] |
| - | [[Category: | + | [[Category: Transferase]] |
| - | [[Category: | + | [[Category: Transit peptide]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:58:44 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 17:58, 3 May 2008
STRUCTURE OF ORNITHINE AMINOTRANSFERASE TRIPLE MUTANT Y85I Y55A G320F
Overview
Ornithine aminotransferase and 4-aminobutyrate aminotransferase are related pyridoxal phosphate-dependent enzymes having different substrate specificities. The atomic structures of these enzymes have shown (i) that active site differences are limited to the steric positions occupied by two tyrosine residues in ornithine aminotransferase and (ii) that, uniquely among related, structurally characterized aminotransferases, the conserved arginine that binds the alpha-carboxylate of alpha-amino acids interacts tightly with a glutamate residue. To determine the contribution of these residues to the specificities of the enzymes, we analyzed site-directed mutants of ornithine aminotransferase by rapid reaction kinetics, x-ray crystallography, and 13C NMR spectroscopy. Mutation of one tyrosine (Tyr-85) to isoleucine, as found in aminobutyrate aminotransferase, decreased the rate of the reaction of the enzyme with ornithine 1000-fold and increased that with 4-aminobutyrate 16-fold, indicating that Tyr-85 is a major determinant of specificity toward ornithine. Unexpectedly, the limiting rate of the second half of the reaction, conversion of ketoglutarate to glutamate, was greatly increased, although the kinetics of the reverse reaction were unaffected. A mutant in which the glutamate (Glu-235) that interacts with the conserved arginine was replaced by alanine retained its regiospecificity for the delta-amino group of ornithine, but the glutamate reaction was enhanced 650-fold, whereas only a 5-fold enhancement of the ketoglutarate reaction rate resulted. A model is proposed in which conversion of the enzyme to its pyridoxamine phosphate form disrupts the internal glutamate-arginine interaction, thus enabling ketoglutarate but not glutamate to be a good substrate.
About this Structure
2BYL is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Determinants of substrate specificity in omega-aminotransferases., Markova M, Peneff C, Hewlins MJ, Schirmer T, John RA, J Biol Chem. 2005 Oct 28;280(43):36409-16. Epub 2005 Aug 11. PMID:16096275 Page seeded by OCA on Sat May 3 20:58:44 2008
