1onz

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|PDB= 1onz |SIZE=350|CAPTION= <scene name='initialview01'>1onz</scene>, resolution 2.40&Aring;
|PDB= 1onz |SIZE=350|CAPTION= <scene name='initialview01'>1onz</scene>, resolution 2.40&Aring;
|SITE=
|SITE=
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|LIGAND= <scene name='pdbligand=968:2-[(7-HYDROXY-NAPHTHALEN-1-YL)-OXALYL-AMINO]-BENZOIC ACID'>968</scene>
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|LIGAND= <scene name='pdbligand=968:2-[(7-HYDROXY-NAPHTHALEN-1-YL)-OXALYL-AMINO]-BENZOIC+ACID'>968</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]], [[1nz7|1NZ7]], [[1ony|1ONY]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1onz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1onz OCA], [http://www.ebi.ac.uk/pdbsum/1onz PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1onz RCSB]</span>
}}
}}
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==Overview==
==Overview==
Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.
Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.
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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: Xin, Z.]]
[[Category: Xin, Z.]]
[[Category: Zinker, B A.]]
[[Category: Zinker, B A.]]
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[[Category: 968]]
 
[[Category: oxalyl-aryl-benzoic acid compound with napthyl moiety anchor inhibitor]]
[[Category: oxalyl-aryl-benzoic acid compound with napthyl moiety anchor inhibitor]]
[[Category: protein tyrosine phosphatase]]
[[Category: protein tyrosine phosphatase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:13:28 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:47:58 2008''

Revision as of 19:48, 30 March 2008

Image:1onz.gif


PDB ID 1onz

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, 1NZ7, 1ONY


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



Oxalyl-aryl-Amino Benzoic acid Inhibitors of PTP1B, compound 8b


Overview

Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.

About this Structure

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

Reference

Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B., Liu G, Szczepankiewicz BG, Pei Z, Janowick DA, Xin Z, Hajduk PJ, Abad-Zapatero C, Liang H, Hutchins CW, Fesik SW, Ballaron SJ, Stashko MA, Lubben T, Mika AK, Zinker BA, Trevillyan JM, Jirousek MR, J Med Chem. 2003 May 22;46(11):2093-103. PMID:12747781

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