1ecv
From Proteopedia
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| - | [[Image:1ecv.jpg|left|200px]] | + | [[Image:1ecv.jpg|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH 5-IODO-2-(OXALYL-AMINO)-BENZOIC ACID''' | + | {{Structure |
| + | |PDB= 1ecv |SIZE=350|CAPTION= <scene name='initialview01'>1ecv</scene>, resolution 1.95Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene> and <scene name='pdbligand=878:5-IODO-2-(OXALYL-AMINO)-BENZOIC ACID'>878</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 COMPLEXED WITH 5-IODO-2-(OXALYL-AMINO)-BENZOIC ACID''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1ECV is a [ | + | 1ECV 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=1ECV OCA]. |
==Reference== | ==Reference== | ||
| - | 2-(oxalylamino)-benzoic acid is a general, competitive inhibitor of protein-tyrosine phosphatases., Andersen HS, Iversen LF, Jeppesen CB, Branner S, Norris K, Rasmussen HB, Moller KB, Moller NP, J Biol Chem. 2000 Mar 10;275(10):7101-8. PMID:[http:// | + | 2-(oxalylamino)-benzoic acid is a general, competitive inhibitor of protein-tyrosine phosphatases., Andersen HS, Iversen LF, Jeppesen CB, Branner S, Norris K, Rasmussen HB, Moller KB, Moller NP, J Biol Chem. 2000 Mar 10;275(10):7101-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10702277 10702277] |
[[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 10:53:49 2008'' |
Revision as of 08:53, 20 March 2008
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| , resolution 1.95Å | |||||||
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| Ligands: | and | ||||||
| Activity: | Protein-tyrosine-phosphatase, with EC number 3.1.3.48 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH 5-IODO-2-(OXALYL-AMINO)-BENZOIC ACID
Contents |
Overview
Protein-tyrosine phosphatases (PTPs) are critically involved in regulation of signal transduction processes. Members of this class of enzymes are considered attractive therapeutic targets in several disease states, e.g. diabetes, cancer, and inflammation. However, most reported PTP inhibitors have been phosphorus-containing compounds, tight binding inhibitors, and/or inhibitors that covalently modify the enzymes. We therefore embarked on identifying a general, reversible, competitive PTP inhibitor that could be used as a common scaffold for lead optimization for specific PTPs. We here report the identification of 2-(oxalylamino)-benzoic acid (OBA) as a classical competitive inhibitor of several PTPs. X-ray crystallography of PTP1B complexed with OBA and related non-phosphate low molecular weight derivatives reveals that the binding mode of these molecules to a large extent mimics that of the natural substrate including hydrogen bonding to the PTP signature motif. In addition, binding of OBA to the active site of PTP1B creates a unique arrangement involving Asp(181), Lys(120), and Tyr(46). PTP inhibitors are essential tools in elucidating the biological function of specific PTPs and they may eventually be developed into selective drug candidates. The unique enzyme kinetic features and the low molecular weight of OBA makes it an ideal starting point for further optimization.
Disease
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]
About this Structure
1ECV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
2-(oxalylamino)-benzoic acid is a general, competitive inhibitor of protein-tyrosine phosphatases., Andersen HS, Iversen LF, Jeppesen CB, Branner S, Norris K, Rasmussen HB, Moller KB, Moller NP, J Biol Chem. 2000 Mar 10;275(10):7101-8. PMID:10702277
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