1no6
From Proteopedia
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|PDB= 1no6 |SIZE=350|CAPTION= <scene name='initialview01'>1no6</scene>, resolution 2.40Å | |PDB= 1no6 |SIZE=350|CAPTION= <scene name='initialview01'>1no6</scene>, resolution 2.40Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=794:2-[(CARBOXYCARBONYL)(1-NAPHTHYL)AMINO]BENZOIC ACID'>794</scene> | + | |LIGAND= <scene name='pdbligand=794:2-[(CARBOXYCARBONYL)(1-NAPHTHYL)AMINO]BENZOIC+ACID'>794</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span> |
|GENE= PTPN1 OR PTP1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= PTPN1 OR PTP1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1nl9|1NL9]], [[1nny|1NNY]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1no6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1no6 OCA], [http://www.ebi.ac.uk/pdbsum/1no6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1no6 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176885 176885]], Insulin resistance, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176885 176885]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Trevillyan, J M.]] | [[Category: Trevillyan, J M.]] | ||
[[Category: Xin, Z.]] | [[Category: Xin, Z.]] | ||
| - | [[Category: 794]] | ||
[[Category: oxamic acid inhibitor bound to p-loop]] | [[Category: oxamic acid inhibitor bound to p-loop]] | ||
[[Category: protein tyrosine phosphatase fold]] | [[Category: protein tyrosine phosphatase fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:33:07 2008'' |
Revision as of 19:33, 30 March 2008
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| , resolution 2.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | PTPN1 OR PTP1B (Homo sapiens) | ||||||
| Activity: | Protein-tyrosine-phosphatase, with EC number 3.1.3.48 | ||||||
| Related: | 1NL9, 1NNY
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 5 Using a Linked-Fragment Strategy
Overview
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.
About this Structure
1NO6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Discovery of a potent, selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy., Szczepankiewicz BG, Liu G, Hajduk PJ, Abad-Zapatero C, Pei Z, Xin Z, Lubben TH, Trevillyan JM, Stashko MA, Ballaron SJ, Liang H, Huang F, Hutchins CW, Fesik SW, Jirousek MR, J Am Chem Soc. 2003 Apr 9;125(14):4087-96. PMID:12670229
Page seeded by OCA on Sun Mar 30 22:33:07 2008
Categories: Homo sapiens | Protein-tyrosine-phosphatase | Single protein | Abad-Zapatero, C. | Ballaron, S J. | Fesik, S W. | Hajduk, P J. | Huang, F. | Hutchins, C W. | Jirousek, M R. | Liang, H. | Liu, G. | Lubben, T. | Pei, Z. | Stashko, M A. | Szczepankiewicz, B G. | Trevillyan, J M. | Xin, Z. | Oxamic acid inhibitor bound to p-loop | Protein tyrosine phosphatase fold
