https://www.abbs.info
E-mail: [email protected]
ISSN
1672-9145
Acta Biochim Biophys Sin
2004, 36(12): 787–792
CN 31-1940/Q
Structural Features of Human Memapsin 2 (b-Secretase) and Their
Biological and Pathological Implications
Lin HONG, Xiangyuan HE, Xiangping HUANG, Wanpin CHANG, and Jordan TANG*
Protein Studies
Program, Oklahoma Medical Research Foundation, University of Oklahoma Health
Science Center, Oklahoma City, Oklahoma 73104, USA
Abstract Memapsin 2 (b-secretase) is the membrane-anchored aspartic protease that initiates
the cleavage of b-amyloid precursor protein (APP) leading to the production of
amyloid-b (Ab), a major factor in the pathogenesis of Alzheimer’s disease (AD).
Since memapsin 2 is a major target for the development of inhibitor drugs for AD,
it has been intensively studied during the past five years. Here we discuss the
structural features of the catalytic/specificity apparatus, transmembrane
domain, cytosolic domain and the implications of these features in the
physiological and pathological roles of this protease.
Key words memapsin
2; b-secretase;
Alzheimer’s disease; b-amyloid; b-amyloid precursor protein; aspartic protease; endocytosis; cellular
trafficking.
—————–
Received: October 13, 2004 Accepted: November 8,
2004
This work was supported by a grant from NIH (No. AG-18933) and an
Alzheimer’s Association Pioneer Award to Prof. Jordan TANG
*Corresponding author: Tel, +1-405-271-7291; Fax, +1-405-271-7249;
E-mail, [email protected]