1TZ2

Crystal structure of 1-aminocyclopropane-1-carboyxlate deaminase complexed with ACC

1TZ2 の概要

• エントリーDOI: 10.2210/pdb1tz2/pdb
• 関連するPDBエントリー: 1RQX 1TYZ
• 分子名称: 1-aminocyclopropane-1-carboxylate deaminase, PYRIDOXAL-5'-PHOSPHATE, 1-AMINOCYCLOPROPANECARBOXYLIC ACID, ... (4 entities in total)
• 機能のキーワード: acc, accd, plp, crystal, complex, substrate, hydrolase
• 由来する生物種: Pseudomonas sp.
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 148251.92

構造登録者

Karthikeyan, S.,Zhou, Q.,Zhao, Z.,Kao, C.L.,Tao, Z.,Robinson, H.,Liu, H.W.,Zhang, H. (登録日: 2004-07-09, 公開日: 2004-11-02, 最終更新日: 2023-08-23)

主引用文献

Karthikeyan, S.,Zhou, Q.,Zhao, Z.,Kao, C.L.,Tao, Z.,Robinson, H.,Liu, H.W.,Zhang, H.
Structural Analysis of Pseudomonas 1-Aminocyclopropane-1-carboxylate Deaminase Complexes: Insight into the Mechanism of a Unique Pyridoxal-5'-phosphate Dependent Cyclopropane Ring-Opening Reaction
Biochemistry, 43:13328-13339, 2004

PubMed Abstract: 1-Aminocyclopropane-1-carboxylate (ACC) deaminase is a pyridoxal 5'-phosphate (PLP) dependent enzyme catalyzing the opening of the cyclopropane ring of ACC to give alpha-ketobutyric acid and ammonia as the products. This ring cleavage reaction is unusual because the substrate, ACC, contains no abstractable alpha-proton and the carboxyl group is retained in the product. How the reaction is initiated to generate an alpha-carbanionic intermediate, which is the common entry for most PLP-dependent reactions, is not obvious. To gain insight into this unusual ring-opening reaction, we have solved the crystal structures of ACC deaminase from Pseudomonas sp. ACP in complex with substrate ACC, an inhibitor, 1-aminocyclopropane-1-phosphonate (ACP), the product alpha-ketobutyrate, and two d-amino acids. Several notable observations of these structural studies include the following: (1) a typically elusive gem-diamine intermediate is trapped in the enzyme complex with ACC or ACP; (2) Tyr294 is in close proximity (3.0 A) to the pro-S methylene carbon of ACC in the gem-diamine complexes, implicating a direct role of this residue in the ring-opening reaction; (3) Tyr294 may also be responsible for the abstraction of the alpha-proton from d-amino acids, a prelude to the subsequent deamination reaction; (4) the steric hindrance precludes accessibility of active site functional groups to the l-amino acid substrates and may account for the stereospecificity of this enzyme toward d-amino acids. These structural data provide evidence favoring a mechanism in which the ring cleavage is induced by a nucleophilic attack at the pro-S beta-methylene carbon of ACC, with Tyr294 as the nucleophile. However, these observations are also consistent with an alternative mechanistic possibility in which the ring opening is acid-catalyzed and may be facilitated by charge relay through PLP, where Tyr294 functions as a general acid. The results of mutagenesis studies corroborated the assigned critical role for Tyr294 in the catalysis.

PubMed: 15491139
DOI: 10.1021/bi048878g

実験手法

X-RAY DIFFRACTION (2.1 Å)