First time at Proteopedia? Click on the green links: they change the 3D image. Click and drag the molecules. Proteopedia is a 3D, interactive encyclopedia of proteins, RNA, DNA and other molecules. With a free user account, you can edit pages in Proteopedia. Visit the Main Page to learn more.

2nta

From Proteopedia

Jump to: navigation, search


2nta, resolution 2.10Å ()
Ligands:
Gene: PTPN1, PTP1B (Homo sapiens)
Activity: Protein-tyrosine-phosphatase, with EC number 3.1.3.48
Related: 2nt7, 2hcx, 2hce, 2hfa
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

Crystal Structure of PTP1B-inhibitor Complex

Publication Abstract from PubMed

The following account describes our systematic effort to replace one of the carboxylate groups of our diacid thiophene PTP1B inhibitors. Active hits were validated using enzymatic assays before pursuing efforts to improve the potency. Only when the C2 carboxylic acid was replaced with another ionizable functional group was reversible and competitive inhibition retained. Use of a tetrazole ring or 1,2,5-thiadiazolidine-3-one-1,1-dioxide as a carboxylate mimetic led to the discovery of two unique starting series that showed improved permeability (PAMPA) and potency of the order of 300nM. The SAR from these efforts underscores some of the major challenges in developing small molecule inhibitors for PTP1B.

Probing acid replacements of thiophene PTP1B inhibitors., Wan ZK, Follows B, Kirincich S, Wilson D, Binnun E, Xu W, Joseph-McCarthy D, Wu J, Smith M, Zhang YL, Tam M, Erbe D, Tam S, Saiah E, Lee J, Bioorg Med Chem Lett. 2007 May 15;17(10):2913-20. Epub 2007 Feb 20. PMID:17336064

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2nta is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Wan ZK, Follows B, Kirincich S, Wilson D, Binnun E, Xu W, Joseph-McCarthy D, Wu J, Smith M, Zhang YL, Tam M, Erbe D, Tam S, Saiah E, Lee J. Probing acid replacements of thiophene PTP1B inhibitors. Bioorg Med Chem Lett. 2007 May 15;17(10):2913-20. Epub 2007 Feb 20. PMID:17336064 doi:10.1016/j.bmcl.2007.02.043

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools