University of Nebraska-Lincoln
736 Hamilton Hall
Lincoln, NE 68588-0304
My lab is searching for antibiotics that inhibit bacterial primase and helicase. These DNA replication enzymes are special to the lagging strand during DNA synthesis. The factors that are driving our search are both the rising numbers of antibiotic-resistant bacterial strains and bioweapons such as Bacillus anthracis and Francisella tularensis. We are using numerous approaches including fluorescence resonance energy transfer (FRET), mass spectrometric peptide mapping, stopped-flow kinetics, computer-aided drug screening. and high-throughput screening of compound libraries.
The enzymes DnaG primase and DnaB helicase are excellent drug targets because they are found in all bacteria, are essential, and are very different from the primase and helicase found in humans. We have already identified the key, controlling step of primer synthesis and are now searching for inhibitors of this process. There appear to be several potential drug binding sites on both of these enzymes and we are now searching for the molecules that bind to those sites to inhibit their action
(1) Using Movie Clips To Teach Chemistry Formally and Informally By: Griep, Mark A.; Mikasen, Marjorie L. Edited by: Nelson, DJ; Grazier, KR; Paglia, J; et al. HOLLYWOOD CHEMISTRY: WHEN SCIENCE MET ENTERTAINMENT Book Series: ACS Symposium Series Volume: 1139 Pages: 199-213 Published: 2013
(2) Shortridge MD, Triplet T, Revesz P, Griep MA, and Powers R, 2011, Bacterial Protein Structures Reveal Phylum Dependent Divergence,Computational Biology & Chemistry 35, 24-33
(3) Larson MA, Griep MA, Bressani R, Chintakayala K, Soultanas P, and Hinrichs SH, 2010, Class-Specific Restrictions Define Primase Interactions with DNA Template and Replicative Helicase Nucleic Acids Research 38, 7167-7178
(4) Larson MA, Bressani R, Sayood K, Corn JE, Berger JM, Griep MA and Hinrichs SH, 2008, Hyperthermophilic Aquifex aeolicus Initiates Primer Synthesis on Trinucleotides Comprised Entirely of Cytosines and/or Guanines, Nucleic Acids Research 36, 5260-5269.