1DY6

Structure of the imipenem-hydrolyzing beta-lactamase SME-1

Summary for 1DY6

• Entry DOI: 10.2210/pdb1dy6/pdb
• Descriptor: CARBAPENEM-HYDROLYSING BETA-LACTAMASE SME-1 (2 entities in total)
• Functional Keywords: hydrolase, lactamase, antibiotic, carbapenem, imipenem
• Biological source: SERRATIA MARCESCENS
• Total number of polymer chains: 2
• Total formula weight: 58772.36

Authors

Sougakoff, W.,L'Hermite, G.,Billy, I.,Guillet, V.,Naas, T.,Nordman, P.,Jarlier, V.,Delettre, J. (deposition date: 2000-01-27, release date: 2001-01-26, Last modification date: 2024-11-13)

Primary citation

Sougakoff, W.,L'Hermite, G.,Billy, I.,Pernot, L.,Guillet, V.,Naas, T.,Nordmann, P.,Jarlier, V.,Delettre, J.
Structure of the Imipenem-Hydrolyzing Class a Beta-Lactamase Sme-1 from Serratia Marcescens.
Acta Crystallogr.,Sect.D, 58:267-, 2002

PubMed 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.

PubMed: 11807251
DOI: 10.1107/S0907444901019606

Experimental method

X-RAY DIFFRACTION (2.13 Å)