1dy6
From Proteopedia
|
STRUCTURE OF THE IMIPENEM-HYDROLYZING BETA-LACTAMASE SME-1
Overview
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.
About this Structure
1DY6 is a Single protein structure of sequence from Serratia marcescens. Active as Beta-lactamase, with EC number 3.5.2.6 Known structural/functional Sites: and . Full crystallographic information is available from OCA.
Reference
Structure of the imipenem-hydrolyzing class A beta-lactamase SME-1 from Serratia marcescens., Sougakoff W, L'Hermite G, Pernot L, Naas T, Guillet V, Nordmann P, Jarlier V, Delettre J, Acta Crystallogr D Biol Crystallogr. 2002 Feb;58(Pt 2):267-74. Epub 2002, Jan 24. PMID:11807251
Page seeded by OCA on Tue Dec 18 14:46:58 2007
