SPECIFICITY DETERMINANTS OF ArmA, A RIBOSOMAL RNA METHYLTRANSFERASE THAT CONFERS ANTIBIOTIC RESISTANCE

Specificity Determinants of ArmA, a Ribosomal RNA Methyltransferase, that confers antibiotic resistance By Tamara Zarubica A Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University Virginia Commonwealth University, 2010 Major Directors: Dr. H. Tonie Wright Professor, Department of Biochemistry and Molecular Biology And Dr. Jason P. Rife Associate Professor, Department of Physiology and Biophysics Bacterial resistance to 4,6-type aminoglycoside antibiotics, which target the 30S ribosomal subunit, has been traced to the arm/rmt family of rRNA methyltransferases. These plasmid-encoded enzymes transfer a methyl group from S-adenosylmethionine to N7 of the buried G1405 in the aminoglycoside binding site of 16S rRNA in the 30S ribosomal subunit. Neither 16S rRNA alone nor intact 70S ribosome is an efficient substrate for armA methyltransferase. To more fully characterize this family of enzymes,