Department of biochemistry and Molecular biology
Alena Fedarovich, PhD
2002 – 2006 Postdoctoral Fellow, Dept. of Biochemistry and Molecular Biology, MUSC
2001 – 2002 Junior Scientist, Dept. of Thyroid Tumors, Research and Clinical Institute
of Radiation Medicine and Endocrinology, Minsk, Belarus
2001 PhD, Institute of Radiobiology of the National Academy of
Sciences of Belarus, Minsk, Belarus
1988 M.Sc., Belarusian State University, Minsk, Belarus
Office: DDB-214 843-876-2303
Protein X-ray crystallography is a powerful technique that provides detailed information on a three-dimensional structure and function of biological macromolecules alone and in complex with other proteins and bioactive ligands. Combined with such biophysical methods as circular dichroism (CD), isothermal titration calorimetry (ITC), dynamic light scattering, and fluorescent spectroscopy as well as with activity or binding assays, structural analysis leads to a better understanding of protein action mechanisms. At present I am involved in study of structure and function of proteins that play an important role in peptidoglycan biosyntheses in bacteria and have crucial role in bacterial resistence to β-lactam antibiotics. The major focus of research is high molecular weight penicillin-binding proteins or transpeptidases from Neisseria gonorrhoeae and mechanisms of their reduced susceptability to β-lactams. Antibiotic resistance that prevails in various strains of pathogenic bacteria demands either new antimicrobials against known targets or new drug targets. Based on recently solved structures of PBP2 (Powell A. et.al, 2009) and PBPA from Mycobacterium tuberculosis (Fedarovich A. et.al, 2012) I am also focused on discovery of new non-β-lactam inhibitors of transpeptidases. To date there is no High-throughput screening (HTS) assay available for a transpeptidase. To address this, a method for HTS of compound libraries was developed using fluorescence polarization, which in tandem with two other activity assays that utilize fluorescence technique, help us to evaluate real inhibitors and study their inhibitory potential (Fedarovich A. et al, 2012).
Recent Publications | Additional Publications
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.
Tomberg J, Temple B, Fedarovich A, Davies C, Nicholas RA. (2012) Interactions involving the X residue of the SXN active site motif with a loop containing the Asp345a insertion are crucial for function of Class B penicillin-binding proteins: mutational and computational analysis of PBP 2 from N. gonorrhoeae. Biochemistry 51:2775-2784.
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. PMID: 20206184.
Huang Y, Fedarovich A, Tomlinson S, Davies C. (2007) Crystal structure of CD59: implications for molecular recognition of the complement proteins C8 and C9 in the membrane-attack complex. Acta Crystallogr D Biol Crystallogr. 63(Pt 6):714-21. Epub 2007 May 15. PubMed PMID: 17505110.
Fedarovich A, Tomberg J, Nicholas RA, Davies C. (2006) Structure of the N-terminal domain of human CEACAM1: binding target of the opacity proteins during invasion of Neisseria meningitidis and N. gonorrhoeae. Acta Crystallogr D Biol Crystallogr. 200662(Pt 9):971-9. Epub 2006 Aug 19. PMID: 16929097.
Nicola G, Fedarovich A, Nicholas RA, Davies C. (2005) A large displacement of the SXN motif of Cys115-modified penicillin-binding protein 5 from Escherichia coli. Biochem J. 392(Pt 1):55-63. PMID: 16038617; PubMed Central PMCID: PMC1317664.
Fedorovich EI, Demidchik IuE. (2002) Triiodothyronine and thyroxin binding to red blood cells in children and adolescents with thyroid cancer. Vopr Onkol. 48(6):661-3. Russian. PMID: 12530259.