Structure-activity relationship of memapsin 2: implications on physiological functions and Alzheimer's disease

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	Structure-activity relationship of memapsin 2: implications on physiological functions and Alzheimer's disease
其他题名	Structure–activity relationship of memapsin 2: implications on physiological functions and Alzheimer's disease
	Li Xiaoman 1; Hong Lin 2; Coughlan Kathleen 3; Wang Liang 4; Cao Liu 1; Tang Jordan 2
	2013
发表期刊	ACTA BIOCHIMICA ET BIOPHYSICA SINICA
ISSN	1672-9145
卷号	45 期号:8 页码:613-621
摘要	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.
其他摘要	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.
关键词	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
收录类别	CSCD
语种	英语
资助项目	[National Institute of Health] ; [Natural National Science Foundation of China] ; [University Innovation Team Support Plan of Liaoning Province]
CSCD记录号	CSCD:4908181
引用统计
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/144161
专题	中国科学院金属研究所
作者单位	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
推荐引用方式 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.