Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

1NL9

Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 12 Using a Linked-Fragment Strategy

Summary for 1NL9
Entry DOI10.2210/pdb1nl9/pdb
Related1NNY 1NO6
DescriptorProtein-tyrosine phosphatase, non-receptor type 1, 2-{[4-(2-ACETYLAMINO-2-PENTYLCARBAMOYL-ETHYL)-NAPHTHALEN-1-YL]-OXALYL-AMINO}-BENZOIC ACID (3 entities in total)
Functional Keywordsprotein tyrosine phosphatase fold, dual-site oxamic acid inhibitor bound to p-loop, hydrolase
Biological sourceHomo sapiens (human)
Cellular locationEndoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side : P18031
Total number of polymer chains1
Total formula weight37899.21
Authors
Primary citationSzczepankiewicz, B.G.,Liu, G.,Hajduk, P.J.,Abad-Zapatero, C.,Pei, Z.,Xin, Z.,Lubben, T.,Trevillyan, J.M.,Stashko, M.A.,Ballaron, S.J.,Liang, H.,Huang, F.,Hutchins, C.W.,Fesik, S.W.,Jirousek, M.R.
Discovery of a Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Using a Linked-Fragment Strategy
J.Am.Chem.Soc., 125:4087-4096, 2003
Cited by
PubMed Abstract: Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that downregulates the insulin receptor. Inhibition of PTP1B is expected to improve insulin action, and the design of small molecule PTP1B inhibitors to treat type II diabetes has received considerable attention. In this work, NMR-based screening identified a nonselective competitive inhibitor of PTP1B. A second site ligand was also identified by NMR-based screening and then linked to the catalytic site ligand by rational design. X-ray data confirmed that the inhibitor bound with the catalytic site in the native, "open" conformation. The final compound displayed excellent potency and good selectivity over many other phosphatases. The modular approach to drug design described in this work should be applicable for the design of potent and selective inhibitors of other therapeutically relevant protein tyrosine phosphatases.
PubMed: 12670229
DOI: 10.1021/ja0296733
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.4 Å)
Structure validation

227344

数据于2024-11-13公开中

PDB statisticsPDBj update infoContact PDBjnumon