Premium
Antibiotic resistance in bacteria: Structure of a novel ss‐DNA metalloenzyme inhibitor
Author(s) -
Pyle Ronald,
Fuson Kerry,
Sutton R. Bryan,
Morales Jorge A.,
Shaw Robert W.
Publication year - 2012
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.26.1_supplement.962.2
Subject(s) - antibiotics , bacteria , dna , chemistry , residue (chemistry) , antibiotic resistance , drug resistance , biochemistry , microbiology and biotechnology , stereochemistry , biology , genetics
β‐Lactam antibiotics are among the most important drugs used to fight bacterial infection. Overuse and misuse of β‐lactam antibiotics has caused the evolution of resistance mechanisms, allowing pathogenic bacteria to survive antibiotic treatment. The major source of resistance to β‐lactam antibiotics occurs through production of enzymes called β‐lactamases capable of catalyzing hydrolysis of the β‐lactam rings in these drug compounds. The metallo‐β‐lactamases have become a major threat due to their broad substrate specificities; there are no clinically useful inhibitors for these metalloenzymes. Previously, we reported the discovery of a 10‐residue single‐stranded DNA (ss‐DNA) aptamer that is a potent inhibitor of the B. cereus 5/B/6 metallo‐β‐lactamase [S.‐K. Kim, C. L. Sims, S. E. Wozniak, S. H. Drude, D. Whitson and R. W. Shaw, Chemical Biology and Drug Design , 74 , 343–348 (2009)]. The ss‐DNA may have a stem‐loop type of secondary structure. We are utilizing molecular mechanics and molecular dynamics calculations to attempt to predict the solution structure of this 10‐residue ss‐DNA aptamer. Furthermore, we have successfully crystallized this aptamer and have shown that the crystals can diffract to 2.5 Å resolution, or better. (TTU‐OTC)