TAILIEUCHUNG - Báo cáo Y học: Enzymic properties of recombinant BACE2

BACE2 (Memapsin 1) is a membrane-bound aspartic pro-tease that is highlyhomologouswithBACE1 (Memapsin 2). While BACE1 processes the amyloid precursor protein (APP) at a key step in generating theb-amyloid peptide and presumably causes Alzheimer’s disease (AD), BACE2 has not been demonstrated to be directly involved in APP pro-cessing, and its physiological functions remain to be vivo, BACE2 is expressed as a precursor protein containing pre-, pro-, protease, transmembrane, and cyto-solic domains/peptides | Eur. J. Biochem. 269 5668-5677 2002 FEBS 2002 doi Enzymic properties of recombinant BACE2 Yong-Tae Kim1 Deborah Downs1 2 Shili Wu1 2 Azar Dashti1 2 Yujun Pan1 Pena Zhai1 2 Xinjuan Wang1 2 3 Xuejun C. Zhang1 and Xinli Lin1 2 4 1 Functional Proteomics Laboratory and Crystallography Program Oklahoma Medical Research Foundation Oklahoma City USA 2ProteomTech Inc. Oklahoma City USA 3Department of Biochemistry and Molecular Biology Peking University Health Science Center Beijing China 4Department of Pathology University of Oklahoma Medical Center Oklahoma City USA BACE2 Memapsin 1 is a membrane-bound aspartic protease that is highly homologous with BACE1 Memapsin 2 . While BACE1 processes the amyloid precursor protein APP at a key step in generating the b-amyloid peptide and presumably causes Alzheimer s disease AD BACE2 has not been demonstrated to be directly involved in APP processing and its physiological functions remain to be determined. In vivo BACE2 is expressed as a precursor protein containing pre- pro- protease transmembrane and cytosolic domains peptides. To detemiine the en ymaiic properties of BACE2 two variants of its pro-protease domain pro-BACE2-T1 PB2-T1 and pro-BACE2-T2 PB2-T2 were constructed. They have henn exireeseed in Escherichia coli as inclusion bodies refolded and purified. Theee Iwo recombinant proteins have the same N terminus but differ at their C-terminal ends PB2-T1 ends at Pro466 on the boundary of the postulated transmembrane domain and PB2-T2 ends at Ser431 close to the homologous ends of other aspartic proteases such as pepsin. White PB2-T1 shares similar substrate specificities with BACE1 and other general aspartic proteases the specificity of PB2-T2 is more constrained apparently preferring to cleave at the NH -terminal side of paired basic residues. Uniike other typical aspartic proteases which are active only under acidic conditions the recombinant BACE2 PB2-T1 was active at a broad pH range. In add

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• genetics
• Structural biochemistry
• Structural Biology
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• Crystal structure
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine