Download MendeleyIsothiazolidinone (Izd) as a Phosphoryl Mimetic in Inhibitors of the Yersinia Pestis Protein Tyrosine Phosphatase Yoph.
Kim, S.E., Bahta, M., Lountos, G.T., Ulrich, R.G., Burke, T.R., Waugh, D.S.(2011) Acta Crystallogr D Biol Crystallogr 67: 639
- PubMed: 21697602
- DOI: https://doi.org/10.1107/S0907444911018610
- Primary Citation of Related Structures:
2YDU - PubMed 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.
Organizational Affiliation:
Chemical Biology Laboratory, National Cancer Institute at Frederick, MD 21702-1201, USA.
