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1nz7

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|PDB= 1nz7 |SIZE=350|CAPTION= <scene name='initialview01'>1nz7</scene>, resolution 2.40&Aring;
|PDB= 1nz7 |SIZE=350|CAPTION= <scene name='initialview01'>1nz7</scene>, resolution 2.40&Aring;
|SITE=
|SITE=
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|LIGAND= <scene name='pdbligand=901:2-[(4-{2-ACETYLAMINO-2-[4-(1-CARBOXY-3-METHYLSULFANYL-PROPYLCARBAMOYL)-BUTYLCARBAMOYL]-ETHYL}-2-ETHYL-PHENYL)-OXALYL-AMINO]-BENZOIC ACID'>901</scene>
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|LIGAND= <scene name='pdbligand=901:2-[(4-{2-ACETYLAMINO-2-[4-(1-CARBOXY-3-METHYLSULFANYL-PROPYLCARBAMOYL)-BUTYLCARBAMOYL]-ETHYL}-2-ETHYL-PHENYL)-OXALYL-AMINO]-BENZOIC+ACID'>901</scene>
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|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]
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|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])
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|DOMAIN=
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|RELATEDENTRY=[[1nl9|1NL9]], [[1nny|1NNY]], [[1no6|1No6]], [[1ony|1ONY]], [[1onz|1ONZ]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nz7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nz7 OCA], [http://www.ebi.ac.uk/pdbsum/1nz7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1nz7 RCSB]</span>
}}
}}
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==Overview==
==Overview==
We have previously reported a novel series of oxalyl-aryl-amino benzoic acid-based, catalytic site-directed, competitive, reversible protein tyrosine phosphatase 1B (PTP1B) inhibitors. With readily access to key intermediates, we utilized a solution phase parallel synthesis approach and rapidly identified a highly potent PTP1B inhibitor (19, K(i)=76 nM) with moderate selectivity (5-fold) over T-cell PTPase (TCPTP) through interacting with a second phosphotyrosine binding site (site 2) in the close proximity to the catalytic site.
We have previously reported a novel series of oxalyl-aryl-amino benzoic acid-based, catalytic site-directed, competitive, reversible protein tyrosine phosphatase 1B (PTP1B) inhibitors. With readily access to key intermediates, we utilized a solution phase parallel synthesis approach and rapidly identified a highly potent PTP1B inhibitor (19, K(i)=76 nM) with moderate selectivity (5-fold) over T-cell PTPase (TCPTP) through interacting with a second phosphotyrosine binding site (site 2) in the close proximity to the catalytic site.
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==Disease==
 
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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.]]
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[[Category: 901]]
 
[[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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:03:42 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:37:33 2008''

Revision as of 19:37, 30 March 2008


PDB ID 1nz7

Drag the structure with the mouse to rotate
, resolution 2.40Å
Ligands:
Gene: PTPN1 OR PTP1B (Homo sapiens)
Activity: Protein-tyrosine-phosphatase, with EC number 3.1.3.48
Related: 1NL9, 1NNY, 1No6, 1ONY, 1ONZ


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



POTENT, SELECTIVE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B USING A SECOND PHOSPHOTYROSINE BINDING SITE, complexed with compound 19.


Overview

We have previously reported a novel series of oxalyl-aryl-amino benzoic acid-based, catalytic site-directed, competitive, reversible protein tyrosine phosphatase 1B (PTP1B) inhibitors. With readily access to key intermediates, we utilized a solution phase parallel synthesis approach and rapidly identified a highly potent PTP1B inhibitor (19, K(i)=76 nM) with moderate selectivity (5-fold) over T-cell PTPase (TCPTP) through interacting with a second phosphotyrosine binding site (site 2) in the close proximity to the catalytic site.

About this Structure

1NZ7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Potent, selective inhibitors of protein tyrosine phosphatase 1B., Xin Z, Oost TK, Abad-Zapatero C, Hajduk PJ, Pei Z, Szczepankiewicz BG, Hutchins CW, Ballaron SJ, Stashko MA, Lubben T, Trevillyan JM, Jirousek MR, Liu G, Bioorg Med Chem Lett. 2003 Jun 2;13(11):1887-90. PMID:12749891

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