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Acyl‐enzyme complex of the class D β‐lactamase OXA‐1 and doripenem
Author(s) -
Schneider Kyle Douglas,
Bonomo Robert,
Leonard David,
Powers Rachel
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.504.9
Subject(s) - doripenem , carbapenem , enzyme , penicillin , substrate (aquarium) , serine , chemistry , beta lactamase , microbiology and biotechnology , stereochemistry , combinatorial chemistry , biochemistry , antibiotics , biology , imipenem , antibiotic resistance , escherichia coli , ecology , gene
The class D β‐lactamase OXA‐1 belongs to the oxacillinase family of lactamase enzymes, OXA‐1 efficiently hydrolyzes penicillin β‐lactams, yet is relatively ineffective at turning over carbapenems. Alternatively, other class D β‐lactamases, such as OXA‐24, are proficient carbapenemase enzymes, but at the expense of their penicillinase activity. To explore this difference in substrate specificity, the structure of OXA‐1 in complex with the clinical carbapenem, doripenem, was determined to 1.4 Åresolution. Initial difference electron density maps contoured at 3σ suggest the presence of the carbapenem in an acyl‐enzyme complex with the catalytic serine (Ser70). Refined data and further studies are expected to yield valuable insight into the cause of the substrate specificity of the oxacillinases in comparison to the carbapenemases.