PDBsum entry 2ydu

Hydrolase

PDB id: 2ydu

Contents

Protein chain

282 a.a.

Ligands

79W

Waters ×276

References listed in PDB file

Key reference

• Title: Isothiazolidinone (izd) as a phosphoryl mimetic in inhibitors of the yersinia pestis protein tyrosine phosphatase yoph.
• Authors: S.E.Kim, M.Bahta, G.T.Lountos, R.G.Ulrich, T.R.Burke, D.S.Waugh.
• Ref.: Acta Crystallogr D Biol Crystallogr, 2011, 67, 639-645.
• PubMed id: 21697602

Abstract

Isothiazolidinone (IZD) heterocycles can act as effective components of protein tyrosine phosphatase (PTP) inhibitors by simultaneously replicating the binding interactions of both a phosphoryl group and a highly conserved water molecule, as exemplified by the structures of several PTP1B-inhibitor complexes. In the first unambiguous demonstration of IZD interactions with a PTP other than PTP1B, it is shown by X-ray crystallography that the IZD motif binds within the catalytic site of the Yersinia pestis PTP YopH by similarly displacing a highly conserved water molecule. It is also shown that IZD-based bidentate ligands can inhibit YopH in a nonpromiscuous fashion at low micromolar concentrations. Hence, the IZD moiety may represent a useful starting point for the development of YopH inhibitors.