Structural features of human memapsin 2 (beta-secretase) and their biological and pathological implications.
Memapsin 2 (beta-secretase) is the membrane-anchored aspartic protease that initiates the cleavage of beta-amyloid precursor protein (APP) leading to the production of amyloid-beta (Abeta), 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.
Hong
Lin
L
Protein Studies Program, Oklahoma Medical Research Foundation, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA.
He
Xiangyuan
X
Huang
Xiangping
X
Chang
Wanpin
W
Tang
Jordan
J
D000544:Alzheimer Disease / Q000209:etiology; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D020134:Catalytic Domain / Q000502:physiology; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D010450:Endopeptidases; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular
D016564:Amyloid beta-Protein Precursor; D008024:Ligands; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human