2Q9J

Crystal structure of the C217S mutant of diaminopimelate epimerase

2Q9J の概要

• エントリーDOI: 10.2210/pdb2q9j/pdb
• 関連するPDBエントリー: 1BWZ 1GQZ 2GKE 2GKJ
• 分子名称: Diaminopimelate epimerase, SULFATE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: c217s mutant, two domains, open conformation of the apo-enzyme, isomerase
• 由来する生物種: Haemophilus influenzae
• 細胞内の位置: Cytoplasm : P44859
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30437.54

構造登録者

Pillai, B.,Cherney, M.,Diaper, C.M.,Sutherland, A.,Blanchard, J.S.,Vederas, J.C. (登録日: 2007-06-12, 公開日: 2007-10-23, 最終更新日: 2024-11-13)

主引用文献

Pillai, B.,Cherney, M.,Diaper, C.M.,Sutherland, A.,Blanchard, J.S.,Vederas, J.C.,James, M.N.G.
Dynamics of catalysis revealed from the crystal structures of mutants of diaminopimelate epimerase.
Biochem.Biophys.Res.Commun., 363:547-553, 2007

PubMed Abstract: Diaminopimelate (DAP) epimerase catalyzes the stereoinversion of ll-DAP to meso-DAP, a precursor of l-lysine and an essential component of the bacterial peptidoglycan. This function is vital to bacteria and the enzyme therefore represents an attractive target for the design of novel anti-bacterials. DAP epimerase belongs to the group of PLP-independent amino acid racemases that function through a rather unusual mechanism involving two cysteines acting in concert as a base (thiolate) and an acid (thiol). We have solved the crystal structures of the apo-forms of DAP epimerase mutants (C73S and C217S) from Haemophilus influenzae at 2.3A and 2.2A resolution, respectively. These structures provide a snapshot of the enzyme in the first step of the catalytic cycle. Comparisons with the structures of the inhibitor-bound form reveal that the enzyme adopts an 'open conformation' in the absence of substrates or inhibitors with the two active site cysteines existing as a thiol-thiolate pair. Substrate binding to the C-terminal domain triggers the closure of the N-terminal domain coupled with tight encapsulation of the ligand, stabilization of the conformation of an active site loop containing Cys73 and expulsion of water molecules with concomitant desolvation of the thiolate base. This structural rearrangement is critical for catalysis.

PubMed: 17889830
DOI: 10.1016/j.bbrc.2007.09.012

実験手法

X-RAY DIFFRACTION (2.2 Å)