Which one among aspartyl protease, metallopeptidase, and artificial metallopeptidase is the most efficient catalyst in peptide hydrolysis?
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.
Bora
Ram Prasad
RP
Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, USA.
Barman
Arghya
A
Zhu
Xiaoxia
X
Ozbil
Mehmet
M
Prabhakar
Rajeev
R
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
D010455:Peptides; D053829:Amyloid Precursor Protein Secretases; D020782:Matrix Metalloproteinases; D007339:Insulysin