3CW8

4-Chlorobenzoyl-CoA Ligase/Synthetase, bound to 4CBA-Adenylate

3CW8 の概要

• エントリーDOI: 10.2210/pdb3cw8/pdb
• 関連するPDBエントリー: 1PG4 1T5D 3CW9
• 分子名称: 4-chlorobenzoyl CoA ligase, 5'-O-[(S)-{[(4-chlorophenyl)carbonyl]oxy}(hydroxy)phosphoryl]adenosine, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: adenylate-forming enzymes, acyl-coa ligase, ligase
• 由来する生物種: Alcaligenes sp.
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55130.16

構造登録者

Reger, A.S.,Cao, J.,Wu, R.,Dunaway-Mariano, D.,Gulick, A.M. (登録日: 2008-04-21, 公開日: 2008-09-02, 最終更新日: 2023-08-30)

主引用文献

Reger, A.S.,Wu, R.,Dunaway-Mariano, D.,Gulick, A.M.
Structural characterization of a 140 degrees domain movement in the two-step reaction catalyzed by 4-chlorobenzoate:CoA ligase.
Biochemistry, 47:8016-8025, 2008

PubMed Abstract: Members of the adenylate-forming family of enzymes play a role in the metabolism of halogenated aromatics and of short, medium, and long chain fatty acids, as well as in the biosynthesis of menaquinone, peptide antibiotics, and peptide siderophores. This family includes a subfamily of acyl- and aryl-CoA ligases that catalyze thioester synthesis through two half-reactions. A carboxylate substrate first reacts with ATP to form an acyl-adenylate. Subsequent to the release of the product PP i, the enzyme binds CoA, which attacks the activated acyl group to displace AMP. Structural and functional studies on different family members suggest that these enzymes alternate between two conformations during catalysis of the two half-reactions. Specifically, after the initial adenylation step, the C-terminal domain rotates by approximately 140 degrees to adopt a second conformation for thioester formation. Previously, we determined the structure of 4-chlorobenzoate:CoA ligase (CBL) in the adenylate forming conformation bound to 4-chlorobenzoate. We have determined two new crystal structures. We have determined the structure of CBL in the original adenylate-forming conformation, bound to the adenylate intermediate. Additionally, we have used a novel product analogue, 4-chlorophenacyl-CoA, to trap the enzyme in the thioester-forming conformation and determined this structure in a new crystal form. This work identifies a novel binding pocket for the CoA nucleotide. The structures presented herein provide the foundation for biochemical analyses presented in the accompanying manuscript in this issue [Wu et al. (2008) Biochemistry 47, 8026-8039]. The complete characterization of this enzyme allows us to provide an explanation for the use of the domain alternation strategy by these enzymes.

PubMed: 18620418
DOI: 10.1021/bi800696y

実験手法

X-RAY DIFFRACTION (2.25 Å)