1w7m
From Proteopedia
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CRYSTAL STRUCTURE OF HUMAN KYNURENINE AMINOTRANSFERASE I IN COMPLEX WITH L-PHE
Overview
The kynurenine pathway has long been regarded as a valuable target for the, treatment of several neurological disorders accompanied by unbalanced, levels of metabolites along the catabolic cascade, kynurenic acid among, them. The irreversible transamination of kynurenine is the sole source of, kynurenic acid, and it is catalyzed by different isoforms of the, 5'-pyridoxal phosphate-dependent kynurenine aminotransferase (KAT). The, KAT-I isozyme has also been reported to possess beta-lyase activity toward, several sulfur- and selenium-conjugated molecules, leading to the proposal, of a role of the enzyme in carcinogenesis associated with environmental, pollutants. We solved the structure of human KAT-I in its 5'-pyridoxal, phosphate and pyridoxamine phosphate forms and in complex with the, competing substrate l-Phe. The enzyme active site revealed a striking, crown of aromatic residues decorating the ligand binding pocket, which we, propose as a major molecular determinant for substrate recognition., Ligand-induced conformational changes affecting Tyr(101) and the, Trp(18)-bearing alpha-helix H1 appear to play a central role in catalysis., Our data reveal a key structural role of Glu(27), providing a molecular, basis for the reported loss of enzymatic activity displayed by the, equivalent Glu --> Gly mutation in KAT-I of spontaneously hypertensive, rats.
About this Structure
1W7M is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Cysteine-S-conjugate beta-lyase, with EC number 4.4.1.13 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Crystal structure of human kynurenine aminotransferase I., Rossi F, Han Q, Li J, Li J, Rizzi M, J Biol Chem. 2004 Nov 26;279(48):50214-20. Epub 2004 Sep 10. PMID:15364907
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