Department of biochemistry and Molecular biology

Christopher Davies, PhD

ProfessorChristopher Davies, PhD
Graduate Program Director
Biochemistry and Molecular Biology

2006-2012     Associate Professor, Dept of Biochemistry & Molecular Biology, MUSC
2001-2006     Assistant Professor, Dept of Biochemistry & Molecular Biology, MUSC
1999-2001     Lecturer, Dept of Biological Sciences, University of Sussex, Brighton, UK
1998              Research Associate, Dept of Structural Biology, St. Jude Research Hospital
1997-1998     Postdoctoral Fellow, Dept of Structural Biology, St. Jude Research Hospital
1992-1996     Postdoctoral Fellow, Dept of Microbiology, Duke University Medical Center
1991-1992     Postdoctoral Fellow, Dept of Biochemistry, University of Bristol, Bristol, UK

Education
1991                Ph.D., University of Bristol, Bristol, UK
1986                B.S., University of Bristol, Bristol, UK

         

Contact Info
Email:
davies@musc.edu
Office: 843-876-2302
Lab: 843-876-2303
Fax: 843-792-8568
DDB-207

Research Interests

Understanding the function of a macromolecule involved in a particular biological process often requires knowledge of its precise three-dimensional structure. This is especially relevant in cases where the molecule has a role in disease. Our group uses the technique of X-ray crystallography, as well as other biochemical approaches, to determine high-resolution structures of macromolecules in a variety of systems. The primary focus of the laboratory is to decipher the structure and function of enzymes involved in peptidoglycan synthesis in bacteria. These include penicillin-binding proteins (PBPs), the well-known molecular targets for ß-lactam antibiotics. Due to the prevalence of antibiotic resistance in bacteria, which poses an increasing threat to public health, these enzymes are of considerable interest. We have recently determined the structure and catalytic mechanism of PBP 5 from E. coli and are now using this system as a vehicle to develop novel antimicrobials directed against pathogenic bacteria. In tandem, we are elucidating many of the molecular mechanisms that underlie antibiotic resistance in Neisseria gonorrhoeae by determining the structures of key proteins involved. The long-term goals of this work are to (a) design new inhibitors against PBPs and (b) via structure determination and biochemical investigation, to develop new molecular targets for antimicrobials.

Recent Publications

1. Solomons JT, Johnsen U, Schönheit P, Davies C. (2013) 3-Phosphoglycerate is an allosteric activator of pyruvate kinase from the hyperthermophilic archaeon Pyrobaculum aerophilum. Biochemistry. Jul 23. [Epub ahead of print] PubMed PMID: 23879743.

2. Tomberg J, Unemo M, Ohnishi M, Davies C & Nicholas RA. (2013) Identification of the amino acids conferring high-level resistance to expanded-spectrum cephalosporins in the penA gene from the Neisseria gonorrhoeae strain H041. Antimicrob Agents Chemother 57(7):3029-36. PMID: 23587946.

3. Tomberg J, Temple B, Fedarovich A, Davies C, Nicholas RA. (2012). A highly conserved interaction involving the middle residue of the SXN active-site motif is crucial for function of class B penicillin-binding proteins: mutational and computational analysis of PBP 2 from N. gonorrhoeae. 51:2775-2784.

4. Fedarovich A, Djordjevic KA, Swanson SM, Peterson YK, Nicholas RA & Davies C. (2012) High-throughput screening for novel inhibitors of Neisseria gonorrhoeae PBP 2. PLoS One 7(9): e44918.

5. Fedarovich A, Nicholas RA & Davies C. (2012) The role of the β5-α11 loop in the active-site dynamics of acylated penicillin-binding protein A from Mycobacterium tuberculosis. J Mol Biol 418:316-330.

6. Tomberg J, Temple B, Fedarovich A, Davies C & Nicholas R.A. (2012) A highly conserved interaction involving the middle residue of the SXN active-site motif is crucial for function of class B penicillin-binding proteins: mutational and computational analysis of PBP 2 from N. gonorrhoeae. Biochemistry 51:2775-2784.

7. Fedarovich A, Nicholas RA & Davies C. (2010) Unusual conformation of the SxN motif in the crystal structure of penicillin-binding protein A from Mycobacterium tuberculosis. J Mol Biol 398:54-65. PMCID: PMC2854034.

8. Tomberg J, Unemo M, Davies C & Nicholas RA. (2010) Molecular and structural analysis of mosaic variants of penicillin-binding protein 2 conferring decreased susceptibility to expanded-spectrum cephalosporins in Neisseria gonorrhoeae: role of epistatic mutations. Biochemistry 49:8062-8070. PMCID: PMC2939205.

9. Nicola G, Tomberg J, Pratt RF, Nicholas RA & Davies C. (2010) Crystal structures of covalent complexes of β-lactam antibiotics with E. coli penicillin-binding protein 5: toward an understanding of antibiotic specificity. Biochemistry 49:8094-8104. PMCID: PMC2947372.

10. Fedarovich A, Nicholas RA & Davies C. (2010) Unusual conformation of the SxN motif in the crystal structure of penicillin-binding protein A from Mycobacterium tuberculosis. J Mol Biol 398(1):54-65. Epub 2010 Mar 3. PubMed PMID: 20206184; PubMed Central PMCID: PMC2854034.

11. Powell AJ, Tomberg J, Deacon AM, Nicholas RA & Davies C. (2009) Crystal structures of penicillin-binding protein 2 from penicillin-susceptible and -resistant strain of N. gonorrhoeae reveal an unexpectedly subtle mechanism for antibiotic resistance. J Biol Chem 284:1202-1212. PMCID: PMC2613624.

12. Zhao S, Duncan M, Tomberg J, Davies C, Unemo M & Nicholas RA. (2009) Genetics of chromosomally mediated intermediate resistance to ceftriaxone and cefixime in Neisseria gonorrhoeae. Antimicrob Agents Chemother 53:3744-3751. PMCID: PMC2737842.

13. Demarse NA, Ponnusamy S, Spicer EK, Apohan E, Baatz JE, Ogretmen B & Davies C. (2009) Direct binding of glyceraldehyde 3-phosphate dehydrogenase to telomeric DNA protects telomeres against chemotherapy-induced rapid degradation. J Mol Biol 394:789-803. PMCID: PMC2789664.

top of page

 
 
 

© 2012  Medical University of South Carolina | Disclaimer