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Acta Crystallogr D Biol Crystallogr. 2002 Feb;58(Pt 2):267-74. Epub 2002 Jan 24.

Structure of the imipenem-hydrolyzing class A beta-lactamase SME-1 from Serratia marcescens.

Author information

1
Laboratoire de Recherche Moléculaire sur les Antibiotiques (LRMA), INSERM EMI0004, Faculté de Médecine Pitié-Salpêtrière, Université Pierre et Marie Curie, 75634 Paris CEDEX 13, France.

Abstract

The structure of the beta-lactamase SME-1 from Serratia marcescens, a class A enzyme characterized by its significant activity against imipenem, has been determined to 2.13 A resolution. The overall structure of SME-1 is similar to that of other class A beta-lactamases. In the active-site cavity, most of the residues found in SME-1 are conserved among class A beta-lactamases, except at positions 104, 105 and 237, where a tyrosine, a histidine and a serine are found, respectively, and at position 238, which is occupied by a cysteine forming a disulfide bridge with the other cysteine residue located at position 69. The crucial role played by this disulfide bridge in SME-1 was confirmed by site-directed mutagenesis of Cys69 to Ala, which resulted in a mutant unable to confer resistance to imipenem and all other beta-lactam antibiotics tested. Another striking structural feature found in SME-1 was the short distance separating the side chains of the active serine residue at position 70 and the strictly conserved glutamate at position 166, which is up to 1.4 A shorter in SME-1 compared with other class A beta-lactamases. Consequently, the SME-1 structure cannot accommodate the essential catalytic water molecule found between Ser70 and Glu166 in the other class A beta-lactamases described so far, suggesting that a significant conformational change may be necessary in SME-1 to properly position the hydrolytic water molecule involved in the hydrolysis of the acyl-enzyme intermediate.

PMID:
11807251
DOI:
10.1107/s0907444901019606
[Indexed for MEDLINE]

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