Isothiazolidinone (IZD) as a phosphoryl mimetic in inhibitors of theYersinia pestisprotein tyrosine phosphatase YopH
Copyright policy )Isothiazolidinone (IZD) as a phosphoryl mimetic in inhibitors of theYersinia pestisprotein tyrosine phosphatase YopH
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.
- National Cancer Institute United States
- National Institute of Health Pakistan
- United States Army Medical Research Institute of Infectious Diseases United States
Models, Molecular, Yersinia pestis, Crystallography, X-Ray, Structure-Activity Relationship, Thiazoles, Biomimetic Materials, Protein Interaction Domains and Motifs, Phosphorylation, Protein Tyrosine Phosphatases, Protein Kinase Inhibitors, Bacterial Outer Membrane Proteins
Models, Molecular, Yersinia pestis, Crystallography, X-Ray, Structure-Activity Relationship, Thiazoles, Biomimetic Materials, Protein Interaction Domains and Motifs, Phosphorylation, Protein Tyrosine Phosphatases, Protein Kinase Inhibitors, Bacterial Outer Membrane Proteins
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).15 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!