Home
This Title All WIREs
WIREs RSS Feed
How to cite this WIREs title:
WIREs Comput Mol Sci
Impact Factor: 8.127

Mechanisms of peptide and phosphoester hydrolysis catalyzed by two promiscuous metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and their synthetic analogues

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

Abstract The hydrolysis of extremely stable peptide and phosphoester bonds by metalloenzymes is of great interest in biotechnology and industry. However, due to various shortcomings only a handful of these enzymes have been used for industrial applications. Therefore, in the last two decades intensive scientific efforts have been made in rational development of small molecules to imitate the activities of natural enzymes. Despite these efforts, their currently available synthetic analogues are inferior in terms of selectivity, catalytic rate, and turnover and the designing of efficient artificial metalloenzymes remains a distant goal. This is a challenging area of research that necessitates a rigorous integration between experiments and theory. The realization of this goal requires knowledge of the catalytic activities of both enzymes and their existing analogues and an effective fusion of that knowledge. This article reviews several studies in which a plethora of computational techniques have been successfully employed to investigate the functioning of two chemically promiscuous mono‐ and binuclear metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and two synthetic analogues. These studies will help us derive fundamental principles of peptide and phosphoester hydrolysis and pave the way to design efficient small molecule catalysts for these reactions. This article is categorized under: Structure and Mechanism > Reaction Mechanisms and Catalysis
Structures of catalysts used for peptide and phosphoester hydrolysis
[ Normal View | Magnified View ]
(a) Proposed mechanism for peptide hydrolysis, (b) direct attack (DA) and catalyst‐assisted (CA) mechanisms for phosphoester hydrolysis, and (c) water‐assisted (WA) mechanism for phosphoester hydrolysis
[ Normal View | Magnified View ]
(a) The QM/MM model of the IP‐HSA complex. (b) Mechanism and energetics for the hydrolysis of site 4 of HSA by IP through the IA mechanism and the LW model
[ Normal View | Magnified View ]
Equilibrated structures of GpdQ: (a) mononuclear form Em, (b) mononuclear BNPP‐bound form Em‐S, (c) active binuclear BNPP‐bound form Eb‐S, (d) substrate‐free form (Eb) of Eb‐S, (e) nucleophile free form (Eb‐S‐H) of Eb‐S, and (f) Asn80Ala mutant form (Eb‐SN80A) of Eb‐S
[ Normal View | Magnified View ]
Equilibrated structures of the active site and six loops of GpdQ
[ Normal View | Magnified View ]
Mechanism for the generation of the binuclear metal center of GpdQ
[ Normal View | Magnified View ]
Mechanism and energetics for the hydrolysis of the Lys‐Gly bond by IDE
[ Normal View | Magnified View ]
Structures of substrates used for peptide and phosphoester hydrolysis
[ Normal View | Magnified View ]

Browse by Topic

Structure and Mechanism > Reaction Mechanisms and Catalysis

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts