title: Mechanisms of peptide hydrolysis by aspartyl and metalloproteases.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, USA. rpr@miami.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Paul
authors.affiliation: Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, USA. rpr@miami.edu.
authors.forename: Arghya
authors.initials: A
authors.lastname: Barman
authors.affiliation: Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, USA. rpr@miami.edu.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Ozbil
authors.affiliation: Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, USA. rpr@miami.edu.
authors.forename: Ram Prasad
authors.initials: RP
authors.lastname: Bora
authors.affiliation: Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, USA. rpr@miami.edu.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, USA. rpr@miami.edu.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Sharma
authors.affiliation: Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, USA. rpr@miami.edu.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Hoffmann
authors.affiliation: Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, USA. rpr@miami.edu.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Prabhakar
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D055162:Biocatalysis; D020134:Catalytic Domain; D002417:Cattle; D006868:Hydrolysis; D007339:Insulysin / Q000737:chemistry / Q000378:metabolism; D007931:Leucyl Aminopeptidase / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry
chemical_list: D008024:Ligands; D010455:Peptides; D053829:Amyloid Precursor Protein Secretases; D007931:Leucyl Aminopeptidase; D007339:Insulysin; D015032:Zinc