Assistant Professor Ph.D. Biochemistry, Cornell University (2002) B.S. Chemistry (A.C.S), UAB (1995) Office: A426B Life Sciences Contact Phone Number: 583-0304 Lab: A428 Life Sciences Lab Phone: 583-0303 Fax Number: 583-0303 E-mail: zac@bmb.uga.edu

Research Interests

My lab is interested in protein structure and function in general, and specifically how enzyme activity is regulated to control metabolic pathways, cell signaling or oxidative stress. A major project in the lab looks at the mechanisms of nucleotide sugar metabolism. To address this we use a combination of techniques, including biochemistry and X-ray crystallography.

Proteoglycans are involved in cell proliferation, migration and adhesion; key steps in both organ morphogenesis and tumor metastasis. Disrupting proteoglycan biosynthesis attenuates tumor growth and progression, thus controlling proteoglycan biosynthesis is a promising strategy for treating cancer. Proteoglycan biosynthesis begins when the sugar xylose is covalently attached to a serine residue in a protein. The donor nucleotide sugar, UDP-xylose, is synthesized from UDP-glucuronic acid in a metabolic pathway controlled by a combination of positive and negative allosteric mechanisms. This complex regulation guarantees steady-state pools of both nucleotide sugars, an important feature since UDP-glucuronic acid is also a sugar donor in Phase II metabolism. In Phase II metabolism, toxins are covalently tagged with glucuronic acid, which targets them for excretion. Ironically, some cancers use this pathway as a drug resistance mechanism to clear potentially useful chemotherapeutics.

Our hope is that by learning how the cell controls nucleotide sugar metabolism, we will identify new therapeutic strategies that target tumor growth, or alter the pharmacological characteristics of drugs by controlling their metabolism.

Selected Publications

• Wood, Z.A., Weaver, L.H., Brown, P.H., Beckett, D. and Matthews, B.W. Co-repressor induced order and biotin repressor dimerization: a case for divergent followed by convergent evolution. Journal of Molecular Biology (2006) 357 509-23 (Cover Illustration).
  
  
• Roberts, B.A., Wood, Z.A., J nsson, T.J., Poole, L.B., and Karplus, P.A. Oxidized and synchrotron cleaved structures of the disulfide redox center in the N-terminal domain of Salmonella typhimurium AhpF. Protein Science (2005) 14, 2414-20.
  
  
• He, M.M., Wood, Z.A., Baase, W.A., Xiao, H. and Matthews, B.W. Alanine-scanning mutagenesis of phage T-4 lysozyme suggests that tertiary context has a dominant effect on b-sheet formation. Protein Science (2004) 13, 2716-24.
  
  
• Wood, Z.A., Poole, L.B. and Karplus, P.A. Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science (2003) 300, 650-3.
  
  
• Wood, Z.A., Schroder, E, Harris, J.R and Poole, L.B. Structure, mechanism and regulation of peroxiredoxins. TiBS (2003) 28, 32-40.
  
  
• Wood, Z.A., Poole, L. B., Hantgan, R.R. and Karplus, P. A. Dimers to doughnuts: redox-sensitive oligomerization of 2-cysteine peroxiredoxins. Biochemistry (2002) 41, 5493-5504.
  
  
• Wood, Z.A., Poole, L. B., and Karplus, P. A. Structure of intact AhpF reveals a mirrored thioredoxin-like active site and implies large domain rotations during catalysis. Biochemistry (2001) 40, 3900-3911 (Journal Cover from 7/02 to 9/02).