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ISSN 1672-9145 Acta Biochim Biophys Sin 2004, 36(12): 787–792 CN 31-1940/Q

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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.

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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]