1no6

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[[Image:1no6.jpg|left|200px]]<br /><applet load="1no6" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1no6.jpg|left|200px]]
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caption="1no6, resolution 2.40&Aring;" />
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'''Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 5 Using a Linked-Fragment Strategy'''<br />
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{{Structure
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|PDB= 1no6 |SIZE=350|CAPTION= <scene name='initialview01'>1no6</scene>, resolution 2.40&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=794:2-[(CARBOXYCARBONYL)(1-NAPHTHYL)AMINO]BENZOIC ACID'>794</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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|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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}}
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'''Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 5 Using a Linked-Fragment Strategy'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1NO6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=794:'>794</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NO6 OCA].
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1NO6 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NO6 OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12670229 12670229]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/12670229 12670229]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Protein-tyrosine-phosphatase]]
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[[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 Feb 21 14:08:10 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:59:24 2008''

Revision as of 10:59, 20 March 2008

Image:1no6.jpg


PDB ID 1no6

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
Coordinates: save as pdb, mmCIF, xml



Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 5 Using a Linked-Fragment Strategy


Contents

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.

Disease

Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]

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

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