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Amino acid sequence and structural comparison of BACE1 and BACE2 using evolutionary trace method.


ABSTRACT: Beta-amyloid precursor protein cleavage enzyme 1 (BACE1) and beta-amyloid precursor protein cleavage enzyme 2 (BACE2), members of aspartyl protease family, are close homologues and have high similarity in their protein crystal structures. However, their enzymatic properties differ leading to disparate clinical consequences. In order to identify the residues that are responsible for such differences, we used evolutionary trace (ET) method to compare the amino acid conservation patterns of BACE1 and BACE2 in several mammalian species. We found that, in BACE1 and BACE2 structures, most of the ligand binding sites are conserved which indicate their enzymatic property of aspartyl protease family members. The other conserved residues are more or less randomly localized in other parts of the structures. Four group-specific residues were identified at the ligand binding site of BACE1 and BACE2. We postulated that these residues would be essential for selectivity of BACE1 and BACE2 biological functions and could be sites of interest for the design of selective inhibitors targeting either BACE1 or BACE2.

SUBMITTER: Mirsafian H 

PROVIDER: S-EPMC4164807 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Amino acid sequence and structural comparison of BACE1 and BACE2 using evolutionary trace method.

Mirsafian Hoda H   Mat Ripen Adiratna A   Merican Amir Feisal AF   Bin Mohamad Saharuddin S  

TheScientificWorldJournal 20140828


Beta-amyloid precursor protein cleavage enzyme 1 (BACE1) and beta-amyloid precursor protein cleavage enzyme 2 (BACE2), members of aspartyl protease family, are close homologues and have high similarity in their protein crystal structures. However, their enzymatic properties differ leading to disparate clinical consequences. In order to identify the residues that are responsible for such differences, we used evolutionary trace (ET) method to compare the amino acid conservation patterns of BACE1 a  ...[more]

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