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B6db references: 15364907

type Journal Article
authors Rossi, F.; Han, Q.; Li, J.; Li, J.; Rizzi, M.
title Crystal structure of human kynurenine aminotransferase I
journal J Biol Chem
sel selected
ui 15364907
year (2004)
volume 279
number 48
pages 50214-20
keywords human
abstract 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 PLP-dependent kynurenine aminotransferase (KATs). The KAT-I isozyme has also been reported to possess b-lyase activity toward several S- and Se- 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 PLP and PMP 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 Tyr101 and the Trp18-bearing a-helix H1, appear to play a central role in catalysis. Our data reveal a key structural role of Glu27, providing a molecular basis for the reported loss of enzymatic activity displayed by the equivalent GluaGly mutation in KAT-I of spontaneously hyperthensive rats.
last changed 2006/04/10 15:36

B6db references