1ph0
From Proteopedia
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|PDB= 1ph0 |SIZE=350|CAPTION= <scene name='initialview01'>1ph0</scene>, resolution 2.20Å | |PDB= 1ph0 |SIZE=350|CAPTION= <scene name='initialview01'>1ph0</scene>, resolution 2.20Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=418:2-{4-[2-(S)-ALLYLOXYCARBONYLAMINO-3-{4-[(2-CARBOXY-PHENYL)-OXALYL-AMINO]-PHENYL}-PROPIONYLAMINO]-BUTOXY}-6-HYDROXY-BENZOIC ACID METHYL ESTER'>418</scene> | + | |LIGAND= <scene name='pdbligand=418:2-{4-[2-(S)-ALLYLOXYCARBONYLAMINO-3-{4-[(2-CARBOXY-PHENYL)-OXALYL-AMINO]-PHENYL}-PROPIONYLAMINO]-BUTOXY}-6-HYDROXY-BENZOIC+ACID+METHYL+ESTER'>418</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=[[1onz|1ONZ]], [[1ony|1ONY]], [[1nl9|1NL9]], [[1nny|1NNY]], [[1n06|1N06]], [[1nz7|1NZ7]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ph0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ph0 OCA], [http://www.ebi.ac.uk/pdbsum/1ph0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ph0 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==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: Szczepankiewicz, B.]] | [[Category: Szczepankiewicz, B.]] | ||
[[Category: Xin, Z.]] | [[Category: Xin, Z.]] | ||
| - | [[Category: 418]] | ||
[[Category: oxalyl-aryl-benzoic acid compound inhibitor]] | [[Category: oxalyl-aryl-benzoic acid compound inhibitor]] | ||
[[Category: protein tyrosine phosphatase 1b]] | [[Category: protein tyrosine phosphatase 1b]] | ||
[[Category: salicylic acid moiety at the second site]] | [[Category: salicylic acid moiety at the second site]] | ||
| - | ''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 22:59:32 2008'' |
Revision as of 19:59, 30 March 2008
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| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | PTPN1 OR PTP1B (Homo sapiens) | ||||||
| Activity: | Protein-tyrosine-phosphatase, with EC number 3.1.3.48 | ||||||
| Related: | 1ONZ, 1ONY, 1NL9, 1NNY, 1N06, 1NZ7
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Non-carboxylic Acid-Containing Inhibitor of PTP1B Targeting the Second Phosphotyrosine Site
Overview
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.
About this Structure
1PH0 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Sun Mar 30 22:59:32 2008
Categories: Homo sapiens | Protein-tyrosine-phosphatase | Single protein | Abad-Zapatero, C. | Ballaron, S J. | Hajduk, P. | Hutchins, C W. | Janowick, D. | Liang, H. | Liu, G. | Pei, Z. | Szczepankiewicz, B. | Xin, Z. | Oxalyl-aryl-benzoic acid compound inhibitor | Protein tyrosine phosphatase 1b | Salicylic acid moiety at the second site
