Research Interests:
My research is in the area of biochemistry, specifically, the relation of structure to function in proteins. For the past several years, I have focused on proteases and peptidases, i.e., enzymes which degrade other proteins, and inhibitors for those enzymes. Current projects focus on the enzyme thimet oligopeptidase (TOP), which terminates the signal of bioactive peptides. We are particularly interested in how the enzyme is able to recognize and act on such a wide variety of substrates. For these studies we collaborate with Jeff Sigman at St. Mary's College and Marc Glucksman at Rosalind Franklin University. Together with Marc Tetel's lab in the Dept of Biological Sciences, we are investigating the control of the enzyme in brain.
Thimet oligopeptidase (Ray, K., Hines,
C.S., Coll-Rodriguez, J., Rodgers, D.W. J.Biol.Chem,.2004 , 279, 20480-20489),
a metalloenzyme
involved in neuroendocrine pathways and blood pressure regulation
Wolfson Team 07/08
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Smith AI, Shrimpton CN, Norman UM, Clarke IJ, Wolfson AJ and Lew RA (2000) Neuropeptidases regulating gonadal function. Biochem Soc Transactions 28: 430-434.
Hall ML, Kohler SJ, *Guth CA and Wolfson AJ.(2003) Advanced Instrumentation Projects for First-Year Biochemistry Laboratory. Biochemistry and Molecular Biology Education 31: 115-118.
Sigman JA, *Edwards SR, Pabon A, Glucksman MJ, and Wolfson AJ. (2003) pH Dependence Studies Provide Insight into the Structure and Mechanism of Thimet Oligopeptidase (EC 3.4.24.15) FEBS Lett 545: 224-228.
Shrimpton CN, Wolfson AJ Smith AI, and Lew RA. (2003) Regulation of the neuropeptide-degrading enzyme, EC3.4.24.15 (thimet oligopeptidase), in cerebrospinal fluid. J Neurosci Res 74: 474-8.
Sigman JA, *Sharky ML, *Walsh ST, Pabon A, Glucksman MJ, and Wolfson AJ.(2003) Involvement of surface cysteines in activity and multimer formation of thimet oligopeptidase Protein Engineering 16: 623-8.
Sigman JA, *Patwa TH, *Tablante AV, *Joseph CD, Glucksman MJ, and Wolfson AJ (2005) Flexibility in substrate recognition by thimet oligopeptidase as revealed by denaturation studies. Biochem J 388: 255-261.
Kolodny NH, *Bauer D, *Bryce K, *Klucevsek K, *Lane A, *Medeiros L, *Mercer W, *Moin S, *Park D, *Peterson J, *Wright J, *Yuen C, Wolfson AJ, and Allen MM (2006) The effect of nitrogen source on cyanophycin synthesis in Synechocystis sp. Stain 6308 J Bacteriol 188: 934-940.
Bruce LA, Sigma JA, *Randall D, *Rodriguez S, *Song MM, *Dai Y, Elmore DE, Pabon A, Glucksman MJ, and Wolfson AJ (2008) Hydrogen bond residue positioning in the 599-611 loop of thimet oligopeptidase is required for substrate selection. FEBS J 276: 5607-5617.
*Moin SS, *Park D, Allen MM, and Wolfson AJ (2005) Regulation of nitrate reductase
activity in a unicellular organism. Experimental Biology Annual Meeting, San
Diego CA, Abs. 509.2
*Stadelmann LE, *Leong R, *Mann-Stadt CF, *Kannabiran DR, Glucksman MJ, Sigman
JA, and Wolfson AJ (2005) Lowered flexibility in thimet oligopeptidase (EC3.4.24.15)
leads to a change in substrate specificity. Experimental Biology Annual Meeting,
San Diego CA, Abs. 528.8
Wolfson AJ, Sigman JA, *Stadelmann LE, *Leong R, *Mann-Stadt CF , *Kannabiran DR, and Glucksman MJ (2005) Substrate Specificity of Thimet Oligopeptidase (EC3.4.24.15) Depends on Loop Flexibility. International Union of Biochemistry Meeting, Budapest, Hungary, Abs. B4-019P.
*Randall D, Sigman JA, *Song M, *Hayes G, Bruce L, Glucksman JA, and Wolfson AJ (2006) Loop region 599-611 determines substrate specificity in thimet oligopeptidase. Experimental Biology Annual Meeting, San Franciso CA, Abs. 75.8
*Srikanthan MR, *Song MM, Bruce LA, *Kua LH, Pabon A, Glucksman MJ, Sigman JA, Elmore DE, and Wolfson AJ (2007) Neuropeptide substrate specificity in thimet oligopeptidase is conferred by glycine residues residing in a loop region. Experimental Biology Annual Meeting, Washington DC, Abs. 805.6
*Kua LH, Cyr NE, Tetel MJ, Chadwick JG, Bruce LA, and Wolfson AJ (2008) Effect of estrogens and progesterone on the distribution and activity of thimet oligopeptidase in rat and mouse brain. Experimental Biology Annual Meeting, San Diego CA Abs. 837.1
*Song MM, Elmore, Sigman JA, Bruce LA, Pabon A, Glucksman MJ, and Wolfson AJ (2008) The 599-611 loop in thimet oligopeptidase modulates substrate selection via hydrogen bonding. Experimental Biology Annual Meeting, San Diego CA Abs. 793.1
*Scognamilla LA, Sigman JA, Glucksman MJ, and Wolfson AJ (2009) Evidence for a conformational change in thimet oligopeptidase and the machinery behind it. Experimental Biology Annual Meeting, New Orleans LA Abs. 502.5
*Dai Y, Cyr NE, Tetel MJ, *Kua LH, Chadwick JG, Bruce LA, and Wolfson AJ (2009) Estradiol regulation and activity of thimet oligopeptidase in the hypothalamus of female mice. Experimental Biology Annual Meeting, New Orleans Abs. 703.5
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