1A7T

METALLO-BETA-LACTAMASE WITH MES

Summary for 1A7T

• Entry DOI: 10.2210/pdb1a7t/pdb
• Descriptor: METALLO-BETA-LACTAMASE, ZINC ION, SODIUM ION, ... (5 entities in total)
• Functional Keywords: hydrolase (beta-lactamase), metallo beta-lactamase, zinc, hydrolase
• Biological source: Bacteroides fragilis
• Cellular location: Periplasm : P25910
• Total number of polymer chains: 2
• Total formula weight: 51473.42

Authors

Fitzgerald, P.M.D.,Wu, J.K.,Toney, J.H. (deposition date: 1998-03-17, release date: 1998-06-17, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.85 Å)