1PS7

Crystal structure of E.coli PdxA

1PS7 の概要

• エントリーDOI: 10.2210/pdb1ps7/pdb
• 関連するPDBエントリー: 1PS6 1PTM
• 分子名称: 4-hydroxythreonine-4-phosphate dehydrogenase, ZINC ION (3 entities in total)
• 機能のキーワード: pyridoxine biosynthesis, oxidoreductase
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm : P19624
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 142173.29

構造登録者

Sivaraman, J.,Li, Y.,Banks, J.,Cane, D.E.,Matte, A.,Cygler, M. (登録日: 2003-06-20, 公開日: 2003-11-04, 最終更新日: 2024-04-03)

主引用文献

Sivaraman, J.,Li, Y.,Banks, J.,Cane, D.E.,Matte, A.,Cygler, M.
Crystal Structure of Escherichia coli PdxA, an Enzyme Involved in the Pyridoxal Phosphate Biosynthesis Pathway
J.Biol.Chem., 278:43682-43690, 2003

PubMed Abstract: Pyridoxal 5'-phosphate is an essential cofactor for many enzymes responsible for the metabolic conversions of amino acids. Two pathways for its de novo synthesis are known. The pathway utilized by Escherichia coli consists of six enzymatic steps catalyzed by six different enzymes. The fourth step is catalyzed by 4-hydroxythreonine-4-phosphate dehydrogenase (PdxA, E.C. 1.1.1.262), which converts 4-hydroxy-l-threonine phosphate (HTP) to 3-amino-2-oxopropyl phosphate. This divalent metal ion-dependent enzyme has a strict requirement for the phosphate ester form of the substrate HTP, but can utilize either NADP+ or NAD+ as redox cofactor. We report the crystal structure of E. coli PdxA and its complex with HTP and Zn2+. The protein forms tightly bound dimers. Each monomer has an alpha/beta/alpha-fold and can be divided into two subdomains. The active site is located at the dimer interface, within a cleft between the two subdomains and involves residues from both monomers. A Zn2+ ion is bound within each active site, coordinated by three conserved histidine residues from both monomers. In addition two conserved amino acids, Asp247 and Asp267, play a role in maintaining integrity of the active site. The substrate is anchored to the enzyme by the interactions of its phospho group and by coordination of the amino and hydroxyl groups by the Zn2+ ion. PdxA is structurally similar to, but limited in sequence similarity with isocitrate dehydrogenase and isopropylmalate dehydrogenase. These structural similarities and the comparison with a NADP-bound isocitrate dehydrogenase suggest that the cofactor binding mode of PdxA is very similar to that of the other two enzymes and that PdxA catalyzes a stepwise oxidative decarboxylation of the substrate HTP.

PubMed: 12896974
DOI: 10.1074/jbc.M306344200

実験手法

X-RAY DIFFRACTION (2.47 Å)