1q6t

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[[Image:1q6t.gif|left|200px]]<br /><applet load="1q6t" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1q6t.gif|left|200px]]
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caption="1q6t, resolution 2.30&Aring;" />
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'''THE STRUCTURE OF PHOSPHOTYROSINE PHOSPHATASE 1B IN COMPLEX WITH COMPOUND 11'''<br />
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{{Structure
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|PDB= 1q6t |SIZE=350|CAPTION= <scene name='initialview01'>1q6t</scene>, resolution 2.30&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=600:6-[4-((2S)-2-(1H-1,2,3-BENZOTRIAZOL-1-YL)-3-{4-[DIFLUORO(PHOSPHONO)METHYL]PHENYL}-2-PHENYLPROPYL)PHENYL]-2-[(1S)-1-METHOXY-3-METHYLBUTYL]QUINOLIN-8-YLPHOSPHONIC ACID'>600</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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'''THE STRUCTURE OF PHOSPHOTYROSINE PHOSPHATASE 1B IN COMPLEX WITH COMPOUND 11'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1Q6T 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=MG:'>MG</scene> and <scene name='pdbligand=600:'>600</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1Q6T OCA].
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1Q6T 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=1Q6T OCA].
==Reference==
==Reference==
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The structural basis for the selectivity of benzotriazole inhibitors of PTP1B., Scapin G, Patel SB, Becker JW, Wang Q, Desponts C, Waddleton D, Skorey K, Cromlish W, Bayly C, Therien M, Gauthier JY, Li CS, Lau CK, Ramachandran C, Kennedy BP, Asante-Appiah E, Biochemistry. 2003 Oct 7;42(39):11451-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14516196 14516196]
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The structural basis for the selectivity of benzotriazole inhibitors of PTP1B., Scapin G, Patel SB, Becker JW, Wang Q, Desponts C, Waddleton D, Skorey K, Cromlish W, Bayly C, Therien M, Gauthier JY, Li CS, Lau CK, Ramachandran C, Kennedy BP, Asante-Appiah E, Biochemistry. 2003 Oct 7;42(39):11451-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14516196 14516196]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Protein-tyrosine-phosphatase]]
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[[Category: selectivity]]
[[Category: selectivity]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:36:28 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:33:49 2008''

Revision as of 11:33, 20 March 2008

Image:1q6t.gif


PDB ID 1q6t

Drag the structure with the mouse to rotate
, resolution 2.30Å
Ligands: and
Gene: PTPN1 OR PTP1B (Homo sapiens)
Activity: Protein-tyrosine-phosphatase, with EC number 3.1.3.48
Coordinates: save as pdb, mmCIF, xml



THE STRUCTURE OF PHOSPHOTYROSINE PHOSPHATASE 1B IN COMPLEX WITH COMPOUND 11


Contents

Overview

Protein tyrosine phosphatase 1B (PTP1B) has been implicated in the regulation of the insulin signaling pathway and represents an attractive target for the design of inhibitors in the treatment of type 2 diabetes and obesity. Inspection of the structure of PTP1B indicates that potent PTP1B inhibitors may be obtained by targeting a secondary aryl phosphate-binding site as well as the catalytic site. We report here the crystal structures of PTP1B in complex with first and second generation aryldifluoromethyl-phosphonic acid inhibitors. While all compounds bind in a previously unexploited binding pocket near the primary binding site, the second generation compounds also reach into the secondary binding site, and exhibit moderate selectivity for PTP1B over the closely related T-cell phosphatase. The molecular basis for the selectivity has been confirmed by single point mutation at position 52, where the two phosphatases differ by a phenylalanine-to-tyrosine switch. These compounds present a novel platform for the development of potent and selective PTP1B inhibitors.

Disease

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

About this Structure

1Q6T is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The structural basis for the selectivity of benzotriazole inhibitors of PTP1B., Scapin G, Patel SB, Becker JW, Wang Q, Desponts C, Waddleton D, Skorey K, Cromlish W, Bayly C, Therien M, Gauthier JY, Li CS, Lau CK, Ramachandran C, Kennedy BP, Asante-Appiah E, Biochemistry. 2003 Oct 7;42(39):11451-9. PMID:14516196

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