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Structure-activity relationship of memapsin 2: implications on physiological functions and Alzheimer's disease
Alternative TitleStructure–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 PublicationACTA BIOCHIMICA ET BIOPHYSICA SINICA
ISSN1672-9145
Volume45Issue:8Pages:613-621
AbstractMemapsin 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 AbstractMemapsin 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.
KeywordAMYLOID 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 ByCSCD
Language英语
Funding Project[National Institute of Health] ; [Natural National Science Foundation of China] ; [University Innovation Team Support Plan of Liaoning Province]
CSCD IDCSCD:4908181
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Document Type期刊论文
Identifierhttp://ir.imr.ac.cn/handle/321006/144161
Collection中国科学院金属研究所
Affiliation1.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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