TY - JOUR
T1 - Mechanisms of peptide hydrolysis by aspartyl and metalloproteases
AU - Paul, Thomas J.
AU - Barman, Arghya
AU - Ozbil, Mehmet
AU - Bora, Ram Prasad
AU - Zhang, Tingting
AU - Sharma, Gaurav
AU - Hoffmann, Zachary
AU - Prabhakar, Rajeev
N1 - Funding Information:
Financial support from the James and Esther King Biomedical Research Program of the Florida State Health Department (DOH grant number 08KN-11) and the National Science Foundation (NSF grant number CHE 1152846) to R. P. is greatly acknowledged. Computational resources from the Center for Computational Science (CCS) at the University of Miami are greatly appreciated. The authors also thank Vindi Jayasinghe Arachchige for help with preparation of the manuscript.
Publisher Copyright:
© 2016 the Owner Societies.
PY - 2016
Y1 - 2016
N2 - Peptide hydrolysis has been involved in a wide range of biological, biotechnological, and industrial applications. In this perspective, the mechanisms of three distinct peptide bond cleaving enzymes, beta secretase (BACE1), insulin degrading enzyme (IDE), and bovine lens leucine aminopeptidase (BILAP), have been discussed. BACE1 is a catalytic Asp dyad [Asp, Asp-] containing aspartyl protease, while IDE and BILAP are mononuclear [Zn(His, His, Glu)] and binuclear [Zn1(Asp, Glu, Asp)-Zn2(Lys, Glu, Asp, Asp)] core possessing metallopeptidases, respectively. Specifically, enzyme-substrate interactions and the roles of metal ion(s), the ligand environment, second coordination shell residues, and the protein environment in the functioning of these enzymes have been elucidated. This information will be useful to design small inhibitors, activators, and synthetic analogues of these enzymes for biomedical, biotechnological, and industrial applications.
AB - Peptide hydrolysis has been involved in a wide range of biological, biotechnological, and industrial applications. In this perspective, the mechanisms of three distinct peptide bond cleaving enzymes, beta secretase (BACE1), insulin degrading enzyme (IDE), and bovine lens leucine aminopeptidase (BILAP), have been discussed. BACE1 is a catalytic Asp dyad [Asp, Asp-] containing aspartyl protease, while IDE and BILAP are mononuclear [Zn(His, His, Glu)] and binuclear [Zn1(Asp, Glu, Asp)-Zn2(Lys, Glu, Asp, Asp)] core possessing metallopeptidases, respectively. Specifically, enzyme-substrate interactions and the roles of metal ion(s), the ligand environment, second coordination shell residues, and the protein environment in the functioning of these enzymes have been elucidated. This information will be useful to design small inhibitors, activators, and synthetic analogues of these enzymes for biomedical, biotechnological, and industrial applications.
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U2 - 10.1039/c6cp02097f
DO - 10.1039/c6cp02097f
M3 - Review article
C2 - 27711373
AN - SCOPUS:84987947880
VL - 18
SP - 24790
EP - 24801
JO - Physical Chemistry Chemical Physics
JF - Physical Chemistry Chemical Physics
SN - 1463-9076
IS - 36
ER -