1c86
From Proteopedia
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| - | [[Image:1c86.gif|left|200px]] | + | [[Image:1c86.gif|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B (R47V,D48N) COMPLEXED WITH 2-(OXALYL-AMINO-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC ACID''' | + | {{Structure |
| + | |PDB= 1c86 |SIZE=350|CAPTION= <scene name='initialview01'>1c86</scene>, resolution 2.3Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=OPA:2-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC ACID'>OPA</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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B (R47V,D48N) COMPLEXED WITH 2-(OXALYL-AMINO-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC ACID''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1C86 is a [ | + | 1C86 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=1C86 OCA]. |
==Reference== | ==Reference== | ||
| - | Structure-based design of a low molecular weight, nonphosphorus, nonpeptide, and highly selective inhibitor of protein-tyrosine phosphatase 1B., Iversen LF, Andersen HS, Branner S, Mortensen SB, Peters GH, Norris K, Olsen OH, Jeppesen CB, Lundt BF, Ripka W, Moller KB, Moller NP, J Biol Chem. 2000 Apr 7;275(14):10300-7. PMID:[http:// | + | Structure-based design of a low molecular weight, nonphosphorus, nonpeptide, and highly selective inhibitor of protein-tyrosine phosphatase 1B., Iversen LF, Andersen HS, Branner S, Mortensen SB, Peters GH, Norris K, Olsen OH, Jeppesen CB, Lundt BF, Ripka W, Moller KB, Moller NP, J Biol Chem. 2000 Apr 7;275(14):10300-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10744717 10744717] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein-tyrosine-phosphatase]] | [[Category: Protein-tyrosine-phosphatase]] | ||
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[[Category: phosphorylation]] | [[Category: phosphorylation]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:21:04 2008'' |
Revision as of 08:21, 20 March 2008
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| , resolution 2.3Å | |||||||
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| Ligands: | |||||||
| Activity: | Protein-tyrosine-phosphatase, with EC number 3.1.3.48 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B (R47V,D48N) COMPLEXED WITH 2-(OXALYL-AMINO-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC ACID
Contents |
Overview
Several protein-tyrosine phosphatases (PTPs) have been proposed to act as negative regulators of insulin signaling. Recent studies have shown increased insulin sensitivity and resistance to obesity in PTP1B knockout mice, thus pointing to this enzyme as a potential drug target in diabetes. Structure-based design, guided by PTP mutants and x-ray protein crystallography, was used to optimize a relatively weak, nonphosphorus, nonpeptide general PTP inhibitor (2-(oxalyl-amino)-benzoic acid) into a highly selective PTP1B inhibitor. This was achieved by addressing residue 48 as a selectivity determining residue. By introducing a basic nitrogen in the core structure of the inhibitor, a salt bridge was formed to Asp-48 in PTP1B. In contrast, the basic nitrogen causes repulsion in other PTPs containing an asparagine in the equivalent position resulting in a remarkable selectivity for PTP1B. Importantly, this was accomplished while retaining the molecular weight of the inhibitor below 300 g/mol.
Disease
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]
About this Structure
1C86 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure-based design of a low molecular weight, nonphosphorus, nonpeptide, and highly selective inhibitor of protein-tyrosine phosphatase 1B., Iversen LF, Andersen HS, Branner S, Mortensen SB, Peters GH, Norris K, Olsen OH, Jeppesen CB, Lundt BF, Ripka W, Moller KB, Moller NP, J Biol Chem. 2000 Apr 7;275(14):10300-7. PMID:10744717
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