title: Which one among aspartyl protease, metallopeptidase, and artificial metallopeptidase is the most efficient catalyst in peptide hydrolysis?
abstract: In this comparative DFT study, the hydrolysis of a peptide bond (Phe1-Phe2) by the following three types of catalysts has been studied: (1) beta-secretase (BACE2), (2) matrix metalloproteinase (MMP) and insulin degrading enzyme (IDE), and (3) [Pd(H(2)O)(4)](2+) (I(MPC)) and [Pd(2)(mu-OH)([18]aneN(6))](3+) (I(DPC)). The computed energetics predict that among these catalysts, the Zn(2+) metal center containing MMP is the most efficient in catalyzing this reaction. The two active site aspartate residues containing BACE2 catalyze this reaction with 5.0 kcal/mol higher barrier than MMP. The substitution of a His ligand with Glu in the metal center of MMP generates the active site of IDE that catalyzes the reaction with a 6.9 kcal/mol higher barrier than MMP. Both artificial peptidases I(MPC) and I(DPC) catalyze this reaction with significantly high barriers of 35.4 and 31.0 kcal/mol, respectively. The computed energetics of all the catalysts are in line with the available experimental and theoretical data.
authors.affiliation: Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, USA.
authors.forename: Ram Prasad
authors.initials: RP
authors.lastname: Bora
authors.forename: Arghya
authors.initials: A
authors.lastname: Barman
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zhu
authors.forename: Mehmet
authors.initials: M
authors.lastname: Ozbil
authors.forename: Rajeev
authors.initials: R
authors.lastname: Prabhakar
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D006868:Hydrolysis; D007339:Insulysin / Q000737:chemistry / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011789:Quantum Theory
chemical_list: D010455:Peptides; D053829:Amyloid Precursor Protein Secretases; D020782:Matrix Metalloproteinases; D007339:Insulysin