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Publication Date

2011-06-22

Availability

UM campus only

Embargo Period

2011-06-22

Degree Name

Master of Science (MS)

Department

Chemistry (Arts and Sciences)

Date of Defense

2011-05-16

First Committee Member

Rajeev Prabhakar

Second Committee Member

Roger M. LeBlanc

Third Committee Member

Burjor Captain

Fourth Committee Member

Stephan C. Schürer

Abstract

In this study, theoretical and computational approaches have been utilized to investigate the mechanisms of natural and artificial metalloproteases. The active sites of most natural metalloproteases contain a tetrahedral zinc center, coordinated by three amino acid residues combinated from His(N), Cys(S), Glu(O), and Asp(O) with a water molecule as the fourth ligand. However, the roles played by the ligands environment in the catalytic functions of enzyme are not clear. In this study, the effects of different ligand combinations (NS2, N2S, N2O, N3, S3, NO2 and NSO) in the mechanism were investigated energy barriers were compared. The machanism and energetics of the substrate bound artificial metalloproteases Ni(II)cyclen (cyclen: 1,4,7,10-tetraazacyclododecane) and Cd(II)cyclen have been investigated. In addition, the mechanism of hydrolysis of Phe-Phe peptide bond catalyzed by another artificial metalloprotease [Pd(H2O)4]2+ has also been studied.

Keywords

mechanism; natural and artificial metalloproteases; theoretical insight

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