1W7N

Crystal structure of human kynurenine aminotransferase I in PMP form

1W7N の概要

• エントリーDOI: 10.2210/pdb1w7n/pdb
• 関連するPDBエントリー: 1W7L 1W7M
• 分子名称: KYNURENINE--OXOGLUTARATE TRANSAMINASE I, 4'-DEOXY-4'-AMINOPYRIDOXAL-5'-PHOSPHATE (3 entities in total)
• 機能のキーワード: kynurenine pathway, kynurenic acid, plp-enzyme, aminotransferase, lyase, multifunctional enzyme, pyridoxal phosphate, transferase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: Q16773
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48176.05

構造登録者

Rossi, F.,Han, Q.,Li, J.,Li, J.,Rizzi, M. (登録日: 2004-09-06, 公開日: 2004-09-08, 最終更新日: 2023-12-13)

主引用文献

Rossi, F.,Han, Q.,Li, J.,Li, J.,Rizzi, M.
Crystal Structure of Human Kynurenine Aminotransferase I
J.Biol.Chem., 279:50214-, 2004

PubMed 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 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.

PubMed: 15364907
DOI: 10.1074/JBC.M409291200

実験手法

X-RAY DIFFRACTION (2.9 Å)