1t4j: Difference between revisions
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|PDB= 1t4j |SIZE=350|CAPTION= <scene name='initialview01'>1t4j</scene>, resolution 2.70Å | |PDB= 1t4j |SIZE=350|CAPTION= <scene name='initialview01'>1t4j</scene>, resolution 2.70Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=FRJ:3-(3,5-DIBROMO-4-HYDROXY-BENZOYL)-2-ETHYL-BENZOFURAN-6-SULFONIC ACID [4-(THIAZOL-2-YLSULFAMOYL)-PHENYL]-AMIDE'>FRJ</scene> | |LIGAND= <scene name='pdbligand=FRJ:3-(3,5-DIBROMO-4-HYDROXY-BENZOYL)-2-ETHYL-BENZOFURAN-6-SULFONIC+ACID+[4-(THIAZOL-2-YLSULFAMOYL)-PHENYL]-AMIDE'>FRJ</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, PTP1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= PTPN1, PTP1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1pty|1PTY]], [[2hnp|2HNP]], [[1t48|1T48]], [[1t49|1T49]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t4j OCA], [http://www.ebi.ac.uk/pdbsum/1t4j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1t4j RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Obesity and type II diabetes are closely linked metabolic syndromes that afflict >100 million people worldwide. Although protein tyrosine phosphatase 1B (PTP1B) has emerged as a promising target for the treatment of both syndromes, the discovery of pharmaceutically acceptable inhibitors that bind at the active site remains a substantial challenge. Here we describe the discovery of an allosteric site in PTP1B. Crystal structures of PTP1B in complex with allosteric inhibitors reveal a novel site located approximately 20 A from the catalytic site. We show that allosteric inhibitors prevent formation of the active form of the enzyme by blocking mobility of the catalytic loop, thereby exploiting a general mechanism used by tyrosine phosphatases. Notably, these inhibitors exhibit selectivity for PTP1B and enhance insulin signaling in cells. Allosteric inhibition is a promising strategy for targeting PTP1B and constitutes a mechanism that may be applicable to other tyrosine phosphatases. | Obesity and type II diabetes are closely linked metabolic syndromes that afflict >100 million people worldwide. Although protein tyrosine phosphatase 1B (PTP1B) has emerged as a promising target for the treatment of both syndromes, the discovery of pharmaceutically acceptable inhibitors that bind at the active site remains a substantial challenge. Here we describe the discovery of an allosteric site in PTP1B. Crystal structures of PTP1B in complex with allosteric inhibitors reveal a novel site located approximately 20 A from the catalytic site. We show that allosteric inhibitors prevent formation of the active form of the enzyme by blocking mobility of the catalytic loop, thereby exploiting a general mechanism used by tyrosine phosphatases. Notably, these inhibitors exhibit selectivity for PTP1B and enhance insulin signaling in cells. Allosteric inhibition is a promising strategy for targeting PTP1B and constitutes a mechanism that may be applicable to other tyrosine phosphatases. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Zhong, M.]] | [[Category: Zhong, M.]] | ||
[[Category: Zhu, J.]] | [[Category: Zhu, J.]] | ||
[[Category: allosteric inhibition protein tyrosine phosphatase 1b]] | [[Category: allosteric inhibition protein tyrosine phosphatase 1b]] | ||
''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 23:51:10 2008'' | ||
