PDBsum entry 2cet

Hydrolase

PDB id: 2cet

Contents

Protein chains

435 a.a.

Ligands

ACT

PGI ×2

Metals

_CA

Waters ×572

References listed in PDB file

Key reference

• Title: Structural, Kinetic, And thermodynamic analysis of glucoimidazole-Derived glycosidase inhibitors.
• Authors: T.M.Gloster, S.Roberts, G.Perugino, M.Rossi, M.Moracci, N.Panday, M.Terinek, A.Vasella, G.J.Davies.
• Ref.: Biochemistry, 2006, 45, 11879-11884. [DOI no: 10.1021/bi060973x]
• PubMed id: 17002288

Abstract

Inhibition of glycosidases has great potential in the quest for highly potent and specific drugs to treat diseases such as diabetes, cancer, and viral infections. One of the most effective ways of designing such compounds is by mimicking the transition state. Here we describe the structural, kinetic, and thermodynamic dissection of binding of two glucoimidazole-derived compounds, which are among the most potent glycosidase inhibitors reported to date, with two family 1 beta-glycosidases. Provocatively, while inclusion of the phenethyl moiety improves binding by a factor of 20-80-fold, this does not appear to result from better noncovalent interactions with the enzyme; instead, improved affinity may be derived from significantly better entropic contributions to binding displayed by the phenethyl-substituted imidazole compound.

Secondary reference #1

• Title: Glycosidase inhibition: an assessment of the binding of 18 putative transition-State mimics.
• Authors: T.M.Gloster, P.Meloncelli, R.V.Stick, D.Zechel, A.Vasella, G.J.Davies.
• Ref.: J Am Chem Soc, 2007, 129, 2345-2354.
• PubMed id: 17279749