1A7T

METALLO-BETA-LACTAMASE WITH MES

1A7T の概要

• エントリーDOI: 10.2210/pdb1a7t/pdb
• 分子名称: METALLO-BETA-LACTAMASE, ZINC ION, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: hydrolase (beta-lactamase), metallo beta-lactamase, zinc, hydrolase
• 由来する生物種: Bacteroides fragilis
• 細胞内の位置: Periplasm : P25910
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51473.42

構造登録者

Fitzgerald, P.M.D.,Wu, J.K.,Toney, J.H. (登録日: 1998-03-17, 公開日: 1998-06-17, 最終更新日: 2024-02-07)

主引用文献

Fitzgerald, P.M.,Wu, J.K.,Toney, J.H.
Unanticipated inhibition of the metallo-beta-lactamase from Bacteroides fragilis by 4-morpholineethanesulfonic acid (MES): a crystallographic study at 1.85-A resolution.
Biochemistry, 37:6791-6800, 1998

PubMed Abstract: As part of a structure-aided effort to design clinically useful inhibitors of metallo-beta-lactamases, the X-ray crystal structure of a complex between the metallo-beta-lactamase from Bacteroides fragilis and 4-morpholinoethanesulfonic acid (MES) has been determined and a model for the structure has been refined to a crystallographic R-factor of 0.151 for data between 10.0- and 1.85-A resolution. Although the binding of MES was an adventitious result of the use of MES as a buffer in the crystallization mixture, MES was subsequently shown to be a competitive inhibitor of the enzyme, with a Ki of 23 +/- 5 mM. MES binds in the same fashion to both of the molecules in the crystallographic asymmetric unit; both direct and solvent-mediated hydrogen bonds to the protein and to the binuclear zinc cluster are observed, involving the oxygens of the sulfonic acid group and the nitrogen of the morpholino ring. In addition, there are hydrophobic interactions between the morpholino ring and residues in the flexible beta-strand of the enzyme between residues 26 and 36. Comparison of this structure with the previously reported unliganded structures of the same enzyme [Concha, N. O., Rasmussen, B. A., Bush, K., and Herzberg, O. (1996) Structure 4, 823-836; Carfi, A., Duée, E., Paul-Soto, R., Galleni, M., Frère, J. -M., and Dideberg, O. (1998) Acta Crystallogr. D54, 47-57] reveals that although the overall conservation of structure in the three different crystal lattices is very high, binding of MES is correlated with a significant change in the conformation of this beta-strand. The flexibility of this beta-strand will be an important consideration in the design of inhibitors of the metallo-beta-lactamases.

PubMed: 9578564
DOI: 10.1021/bi9730339

実験手法

X-RAY DIFFRACTION (1.85 Å)