faculty
Susan Wang

Susan Wang

Associate Professor

suewang@vetmed.wsu.edu

Office
Room: BLS 445
Phone: 509-335-7714

Lab
Room: BLS 440
Phone: 509-335-7709

Courses Taught

  • MBioS 305: General Microbiology Lecture

 

Research & Interests

The “radical SAM (S-adenosyl-L-methionine)” enzyme superfamily was initially described in 2001. The members of this superfamily, numbering in the thousands, catalyze a wide variety of reactions, most of which have not been characterized. The few radical SAM enzymes that have been studied share only two obvious characteristics. 1 - They each contain an unusual iron-sulfur ([4Fe-4S]) cluster in which three ligands to the cluster are cysteine residues from the protein, while the fourth ligand is SAM. These cysteine residues are found in a CXXXCXXC amino acid motif considered to be the hallmark of this superfamily. 2 - They utilize a 5'-deoxyadenosyl (Ado-CH2•) radical generated from the homolytic cleavage of SAM to abstract a hydrogen atom from the appropriate substrate. Our lab is interested in the fundamental mechanistic issues surrounding the subfamily of radical SAM enzymes believed to catalyze interesting and difficult methyl transfer reactions required by some organisms for antibiotic biosynthesis. Little is understood about these enzymes, but like many other methyltransferases, they reportedly require methylcobalamin (a derivative of vitamin B12) for activity. Since either SAM or methylcobalamin can function as a methyl transfer agent, we wish to determine whether these proteins require one or both as cofactors (or perhaps substrates) in catalysis. We combine a variety of techniques spanning molecular biology, organic synthesis, nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopies, and protein chemistry. These studies will provide further insight into the biological pathways used for antibiotic synthesis, thus facilitating the design of new antibiotic compounds and leading to the improvement of industrial processes used for large-scale antibiotic production.

Select Publications

  • Wang SC, Frey PA (2007) Binding energy in the one-electron reductive cleavage of S-adenosylmethionine in lysine 2,3-aminomutase, a radical SAM enzyme. Biochemistry. 46(45), 12889-95 PMID: 17944492 PMCID: PMC2553252
  • Wang SC, Johnson WH Jr, Czerwinski RM, Stamps SL, Whitman CP (2007) Kinetic and stereochemical analysis of YwhB, a 4-oxalocrotonate tautomerase homologue in Bacillus subtilis: mechanistic implications for the YwhB- and 4-oxalocrotonate tautomerase-catalyzed reactions. Biochemistry 46(42), 11919-29 PMID: 17902707 PMCID: PMC2531070
  • Wang SC, Frey PA. (2007) S-adenosylmethionine as an oxidant: the radical SAM superfamily. Trends Biochem Sci. 32(3), 101-10 PMID: 17291766
  • Golubkov PA, Johnson WH Jr, Czerwinski RM, Person MD, Wang SC, Whitman CP, Hackert ML (2006) Inactivation of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor by 2-oxo-4-phenyl-3-butynoate. Bioorg Chem. 34(4), 183-99 PMID: 16780921
  • Goodman JL, Wang S, Alam S, Ruzicka FJ, Frey PA, Wedekind JE (2004) Ornithine cyclodeaminase: structure, mechanism of action, and implications for the mu-crystallin family. Biochemistry. 43(44), 13883-91 PMID: 15518536
  • Johnson WH Jr, Wang SC, Stanley TM, Czerwinski RM, Almrud JJ, Poelarends GJ, Murzin AG, Whitman CP (2004) 4-Oxalocrotonate tautomerase, its homologue YwhB, and active vinylpyruvate hydratase: synthesis and evaluation of 2-fluoro substrate analogues. Biochemistry 43(32), 10490-501 PMID: 15301547
  • Alam S, Wang SC, Ruzicka FJ, Frey PA, Wedekind JE (2004) Crystallization and X-ray diffraction analysis of ornithine cyclodeaminase from Pseudomonas putida. Acta Crystallogr D Biol Crystallogr. 60(Pt 5), 941-4. PMID: 15103146
  • Azurmendi HF, Wang SC, Massiah MA, Poelarends GJ, Whitman CP, Mildvan AS (2004) The roles of active-site residues in the catalytic mechanism of trans-3-chloroacrylic acid dehalogenase: a kinetic, NMR, and mutational analysis. Biochemistry 43(14), 4082-91 PMID: 15065850
  • Wang SC, Person MD, Johnson WH Jr, Whitman CP (2003) Reactions of trans-3-chloroacrylic acid dehalogenase with acetylene substrates: consequences of and evidence for a hydration reaction. Biochemistry 42(29), 8762-73 PMID: 12873137
  • Wang SC, Johnson WH Jr, Whitman CP (2003) The 4-oxalocrotonate tautomerase- and YwhB-catalyzed hydration of 3E-haloacrylates: implications for the evolution of new enzymatic activities. J Am Chem Soc. 125(47), 14282-3 PMID: 14624569
  • Wang SC, Johnson WH Jr, Czerwinski RM, Whitman CP (2004) Reactions of 4-oxalocrotonate tautomerase and YwhB with 3-halopropiolates: analysis and implications. Biochemistry. 43(3), 748-58 PMID: 14730980
  • Shine NR, Wang SC, Konopka K, Burks EA, Düzgüneş N, Whitman CP (2002) Secretory leukocyte protease inhibitor: inhibition of human immunodeficiency virus-1 infection of monocytic THP-1 cells by a newly cloned protein. Bioorg Chem 30(4), 249-63 PMID: 12392704
  • Almrud JJ, Kern AD, Wang SC, Czerwinski RM, Johnson WH Jr, Murzin AG, Hackert ML, Whitman CP (2002) The Crystal Structure of YdcE, a 4-Oxalocrotonate Tautomerase Homologue from Escherichia coli, Confirms the Structural Basis for Oligomer Diversity Biochemistry 41(40), 12010-24 PMID: 12356301
  • Stamps SL, Taylor AB, Wang SC, Hackert ML, Whitman CP (2000) Mechanism of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor: properties of the P1G, P1A, Y95F, and N97A mutants. Biochemistry 39(32), 9671-8 PMID: 10933783