1D7U

Crystal structure of the complex of 2,2-dialkylglycine decarboxylase with LCS

1D7U の概要

• エントリーDOI: 10.2210/pdb1d7u/pdb
• 関連するPDBエントリー: 1D7R 1D7S 1D7V
• 分子名称: PROTEIN (2,2-DIALKYLGLYCINE DECARBOXYLASE (PYRUVATE)), SODIUM ION, POTASSIUM ION, ... (5 entities in total)
• 機能のキーワード: enzyme complexes, catalytic mechanism, decarboxylation inhibitor, lyase
• 由来する生物種: Burkholderia cepacia
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46888.63

構造登録者

Malashkevich, V.N.,Toney, M.D.,Strop, P.,Keller, J.,Jansonius, J.N. (登録日: 1999-10-19, 公開日: 1999-11-19, 最終更新日: 2023-08-09)

主引用文献

Malashkevich, V.N.,Strop, P.,Keller, J.W.,Jansonius, J.N.,Toney, M.D.
Crystal structures of dialkylglycine decarboxylase inhibitor complexes.
J.Mol.Biol., 294:193-200, 1999

PubMed Abstract: The crystal structures of four inhibitor complexes of dialkylglycine decarboxylase are reported. The enzyme does not undergo a domain closure, as does aspartate aminotransferase, upon inhibitor binding. Two active-site conformations have been observed in previous structures that differ in alkali metal ion content, and two active-site conformations have been shown to coexist in solution when a single type of metal ion is present. There is no indication of coexisting conformers in the structures reported here or in the previously reported structures, and the observed conformation is that expected based on the presence of potassium in the enzyme. Thus, although two active-site conformations coexist in solution, a single conformation, corresponding to the more active enzyme, predominates in the crystal. The structure of 1-aminocyclopropane-1-carboxylate bound in the active site shows the aldimine double bond to the pyridoxal phosphate cofactor to be fully out of the plane of the coenzyme ring, whereas the Calpha-CO2(-) bond lies close to it. This provides an explanation for the observed lack of decarboxylation reactivity with this amino acid. The carboxylate groups of both 1-aminocyclopropane-1-carboxylate and 5'-phosphopyridoxyl-2-methylalanine interact with Ser215 and Arg406 as previously proposed. This demonstrates structurally that alternative binding modes, which constitute substrate inhibition, occur in the decarboxylation half-reaction. The structures of d and l-cycloserine bound to the active-site show that the l-isomer is deprotonated at C(alpha), presumably by Lys272, while the d-isomer is not. This difference explains the approximately 3000-fold greater potency of the l versus the d-isomer as a competitive inhibitor of dialkylglycine decarboxylase.

PubMed: 10556038
DOI: 10.1006/jmbi.1999.3254

実験手法

X-RAY DIFFRACTION (1.95 Å)