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spinqualitylabelsall models 1tz2, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Overview

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.

About this Structure

1TZ2 is a Single protein structure of sequence from Pseudomonas sp. with PLP and 1AC as ligands. Active as 1-aminocyclopropane-1-carboxylate deaminase, with EC number 3.5.99.7 Full crystallographic information is available from OCA.

Reference

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., Karthikeyan S, Zhou Q, Zhao Z, Kao CL, Tao Z, Robinson H, Liu HW, Zhang H, Biochemistry. 2004 Oct 26;43(42):13328-39. PMID:15491139

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