Structure-activity relationship of memapsin 2: implications on physiological functions and Alzheimer's disease | |
Alternative Title | Structure–activity relationship of memapsin 2: implications on physiological functions and Alzheimer's disease |
Li Xiaoman1; Hong Lin2; Coughlan Kathleen3; Wang Liang4; Cao Liu1; Tang Jordan2 | |
2013 | |
Source Publication | ACTA BIOCHIMICA ET BIOPHYSICA SINICA
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ISSN | 1672-9145 |
Volume | 45Issue:8Pages:613-621 |
Abstract | Memapsin 2 (BACE1, -secretase), a membrane aspartic protease, functions in the cleavage of the type I transmembrane protein, -amyloid precursor protein (APP), leading to the production of amyloid (A) in the brain. Since A is closely associated with the pathogenesis of Alzheimers disease, understanding the biological function, particularly the catalytic activities of memapsin 2, would assist in a better understanding of the disease and the development of its inhibitors. The transmembrane and cytosolic domains of memapsin 2 function in cellular transport and localization, which are important regulatory mechanisms for its activity. The catalytic ectodomain contains a long substrate cleft that is responsible for substrate recognition, specificity, and peptide bond hydrolysis. The substrate cleft accommodates 11 residues of the substrate in separate binding subsites. Besides APP, a number of membrane proteins have been reported to be substrates of memapsin 2. The elucidation for the specificity of these subsites and the amino acid sequences surrounding the memapsin 2 cleavage site in these proteins has led to the establishment of a predictive model that can quantitatively estimate the efficiency of cleavage for any potential substrates. Such tools may be employed for future studies of memapsin 2 about its biological function. Herein, we review the current knowledge on the structurefunction relationship of memapsin 2 and its relationship in the biological function. |
Other Abstract | Memapsin 2 (BACE1, β-secretase), a membrane aspartic protease, functions in the cleavage of the type I transmembrane protein, β-amyloid precursor protein (APP), leading to the production of amyloid β (Aβ) in the brain. Since Aβ is closely associated with the pathogenesis of Alzheimer's disease, understanding the biological function, particularly the catalytic activities of memapsin 2, would assist in a better understanding of the disease and the development of its inhibitors. The transmembrane and cytosolic domains of memapsin 2 function in cellular transport and localization, which are important regulatory mechanisms for its activity. The catalytic ectodomain contains a long substrate cleft that is responsible for substrate recognition, specificity, and peptide bond hydrolysis. The substrate cleft accommodates 11 residues of the substrate in separate binding subsites. Besides APP, a number of membrane proteins have been reported to be substrates of memapsin 2. The elucidation for the specificity of these subsites and the amino acid sequences surrounding the memapsin 2 cleavage site in these proteins has led to the establishment of a predictive model that can quantitatively estimate the efficiency of cleavage for any potential substrates. Such tools may be employed for future studies of memapsin 2 about its biological function. Herein, we review the current knowledge on the structure–function relationship of memapsin 2 and its relationship in the biological function. |
Keyword | AMYLOID PRECURSOR PROTEIN BETA-SECRETASE BACE1 GATED SODIUM-CHANNELS CLEAVING ENZYME GGA PROTEINS ASPARTYL PROTEASE NEURONAL-ACTIVITY GENETIC DELETION CYTOSOLIC DOMAIN ALPHA-SECRETASE memapsin 2 BACE1 beta-amyloid subsite specificity activity prediction |
Indexed By | CSCD |
Language | 英语 |
Funding Project | [National Institute of Health] ; [Natural National Science Foundation of China] ; [University Innovation Team Support Plan of Liaoning Province] |
CSCD ID | CSCD:4908181 |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.imr.ac.cn/handle/321006/144161 |
Collection | 中国科学院金属研究所 |
Affiliation | 1.上海市地震局 2.Oklahoma Med Res Fdn, Prot Studies Program, Oklahoma City, OK 73104 USA 3.中国科学院上海生命科学研究院 4.中国科学院大连化学物理研究所 5.中国科学院金属研究所 |
Recommended Citation GB/T 7714 | Li Xiaoman,Hong Lin,Coughlan Kathleen,et al. Structure-activity relationship of memapsin 2: implications on physiological functions and Alzheimer's disease[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2013,45(8):613-621. |
APA | Li Xiaoman,Hong Lin,Coughlan Kathleen,Wang Liang,Cao Liu,&Tang Jordan.(2013).Structure-activity relationship of memapsin 2: implications on physiological functions and Alzheimer's disease.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,45(8),613-621. |
MLA | Li Xiaoman,et al."Structure-activity relationship of memapsin 2: implications on physiological functions and Alzheimer's disease".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 45.8(2013):613-621. |
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