1ph0

File:1ph0.gif

spinqualitylabelsall models 1ph0, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Non-carboxylic Acid-Containing Inhibitor of PTP1B Targeting the Second Phosphotyrosine Site

OverviewOverview

Protein tyrosine phosphatase (PTPase) 1B (PTP1B) has been implicated as a, key negative regulator of both insulin and leptin signaling cascades. We, identified several salicylic acid-based ligands for the second, phosphotyrosine binding site of PTP1B using a NMR-based screening., Structure-based linking with a catalytic site-directed, oxalylarylaminobenzoic acid-based pharmacophore led to the identification, of a novel series of potent PTP1B inhibitors exhibiting 6-fold selectivity, over the highly homologous T-cell PTPase (TCPTP) and high selectivity over, other phosphatases.

DiseaseDisease

Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]

About this StructureAbout this Structure

1PH0 is a Single protein structure of sequence from Homo sapiens with 418 as ligand. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.

ReferenceReference

Selective protein tyrosine phosphatase 1B inhibitors: targeting the second phosphotyrosine binding site with non-carboxylic acid-containing ligands., Liu G, Xin Z, Liang H, Abad-Zapatero C, Hajduk PJ, Janowick DA, Szczepankiewicz BG, Pei Z, Hutchins CW, Ballaron SJ, Stashko MA, Lubben TH, Berg CE, Rondinone CM, Trevillyan JM, Jirousek MR, J Med Chem. 2003 Jul 31;46(16):3437-40. PMID:12877578

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