2cni
STRUCTURAL INSIGHTS INTO THE DESIGN OF NONPEPTIDIC ISOTHIAZOLIDINONE-CONTAINING INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B
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OverviewOverview
Structural analyses of the protein-tyrosine phosphatase 1B (PTP1B) active, site and inhibitor complexes have aided in optimization of a peptide, inhibitor containing the novel (S)-isothiazolidinone (IZD) phosphonate, mimetic. Potency and permeability were simultaneously improved by, replacing the polar peptidic backbone of the inhibitor with nonpeptidic, moieties. The C-terminal primary amide was replaced with a benzimidazole, ring, which hydrogen bonds to the carboxylate of Asp(48), and the N, terminus of the peptide was replaced with an aryl sulfonamide, which, hydrogen bonds to Asp(48) and the backbone NH of Arg(47) via a water, molecule. Although both substituents retain the favorable hydrogen bonding, network of the peptide scaffold, their aryl rings interact weakly with the, ... [(full description)]
About this StructureAbout this Structure
2CNI is a [Single protein] structure of sequence from [Homo sapiens] with MG and IZF as [ligands]. Active as [Protein-tyrosine-phosphatase], with EC number [3.1.3.48]. Structure known Active Site: AC1. Full crystallographic information is available from [OCA].
ReferenceReference
Structural insights into the design of nonpeptidic isothiazolidinone-containing inhibitors of protein-tyrosine phosphatase 1B., Ala PJ, Gonneville L, Hillman M, Becker-Pasha M, Yue EW, Douty B, Wayland B, Polam P, Crawley ML, McLaughlin E, Sparks RB, Glass B, Takvorian A, Combs AP, Burn TC, Hollis GF, Wynn R, J Biol Chem. 2006 Dec 8;281(49):38013-21. Epub 2006 Oct 6. PMID:17028182
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