Member and Program Head, Protein
Studies Research Program
J.G. Puterbaugh Chair in Medical Research
Adjunct Professor, Department of
Biochemistry and Molecular Biology, University of Oklahoma Health Sciences
Center
Mailing Address
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104
Contact Information
Phone: (405) 271-6673
Fax: (405) 271-3980
E-mail: [email protected]
Research Interests:
My main research interest is in the
structure and biological functions of aspartic proteases. An area of current
focus is on the human memapsin 2 and Alzheimer's disease. Our group recently
cloned memapsin 2 and identified it to be b-secretase, which is known to
hydrolyze b-amyloid precursor protein. The accumulation of the hydrolytic
product of this enzyme in the brain ultimately leads to the onset of
Alzheimer's disease. We are interested in developing inhibitors for memapsin 2,
which will hopefully lead to drugs for the treatment of the disease. To
facilitate this goal, we have recently solved the crystal structure of memapsin
2 with a designed inhibitor in its active site. Future work is aimed at making
the inhibitor smaller so it can penetrate the blood-brain barrier and
specifically for memapsin 2, so the side effects may be limited. In addition,
we are interested in learning the physiological functions of memapsin 2 in
human brain and other organs.
Selected Publications:
Loy JA, Lin X, Schenone M, Castellino FJ, Zhang XC and Tang J.
Domain interactions between streptokinase and human plasminogen. Biochemistry
40:14686-14695, 2001. [Abstract]
Turner RT 3rd, Koelsch G, Hong L, Castenheira P, Ermolieff J, Ghosh
AK, Tang J, Castenheira P, and Ghosh A. Subsite specificity of memapsin 2
(beta-secretase): implications for inhibitor design. Biochemistry
40:10001-10006, 2001. [Abstract]
Judd DA, Nettles JH, Nevins N, Snyder JP, Liotta DC, Tang J,
Ermolieff J, Schinazi RF and Hill CL. Polyoxometalate HIV-1 protease
inhibitors. A new mode of protease inhbition. J. Am. Chem. Soc. 123:886-897,
2001. [Abstract]
Ghosh AK, Bilcer G, Harwood C, Kawahama R, Shin D, Hussain KA, Hong
L, Loy JA, Nguyen C, Koelsch G, Ermolieff J and Tang J. Structure-based design:
potent inhibitors of human brain memapsin 2 (beta-secretase) J. Med. Chem.
44:2865-2868, 2001. [Abstract]
Ermolieff J, Loy JA, Koelsch G and Tang J. Proteolytic activation
of recombinant pro-memapsin 2 (pro-beta-secretase) studied with new fluorogenic
substrates. Biochemistry 39:12450-12456, 2000. [Abstract]
Ghosh AK, Shin D, Downs D, Koelsch G, Lin X, Ermolieff J and Tang
J. Design of potent inhibitors for human brain memapsin 2 (b-secretase). J Am
Chem Soc 122:3522-3523, 2000.
Hong L, Zhang XC, Hartsuck JA and Tang J. Crystal structure of an
in vivo HIV-1 protease mutant in complex with saquinavir: insights into the
mechanisms of drug resistance. Protein Sci 9:1898-1904, 2000. [Abstract]
Hong L, Koelsch G, Lin X, Wu S, Terzyan S, Ghosh AK, Zhang XC and
Tang J. Structure of the protease domain of memapsin 2 (beta-secretase)
complexed with inhibitor. Science 290:150-153, 2000. [Abstract]
Koelsch G, Tang J, Loy JA, Monod M, Jackson K, Foundling SI and Lin
X. Enzymic characteristics of secreted aspartic proteases of Candida albicans.
Biochim Biophys Acta 1480:117-131, 2000. [Abstract]
Lin X, Koelsch G, Wu S, Downs D, Dashti A and Tang J. Human
aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid
precursor protein. Proc Natl Acad Sci (USA) 97:1456-1460, 2000. [Abstract]