2cm2
From Proteopedia
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|SITE= <scene name='pdbsite=AC1:Mpd+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Mpd+Binding+Site+For+Chain+A'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene> | |LIGAND= <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2cm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cm2 OCA], [http://www.ebi.ac.uk/pdbsum/2cm2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2cm2 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Crystal structures of protein-tyrosine phosphatase 1B in complex with compounds bearing a novel isothiazolidinone (IZD) heterocyclic phosphonate mimetic reveal that the heterocycle is highly complementary to the catalytic pocket of the protein. The heterocycle participates in an extensive network of hydrogen bonds with the backbone of the phosphate-binding loop, Phe(182) of the flap, and the side chain of Arg(221). When substituted with a phenol, the small inhibitor induces the closed conformation of the protein and displaces all waters in the catalytic pocket. Saturated IZD-containing peptides are more potent inhibitors than unsaturated analogs because the IZD heterocycle and phenyl ring directly attached to it bind in a nearly orthogonal orientation with respect to each other, a conformation that is close to the energy minimum of the saturated IZD-phenyl moiety. These results explain why the heterocycle is a potent phosphonate mimetic and an ideal starting point for designing small nonpeptidic inhibitors. | Crystal structures of protein-tyrosine phosphatase 1B in complex with compounds bearing a novel isothiazolidinone (IZD) heterocyclic phosphonate mimetic reveal that the heterocycle is highly complementary to the catalytic pocket of the protein. The heterocycle participates in an extensive network of hydrogen bonds with the backbone of the phosphate-binding loop, Phe(182) of the flap, and the side chain of Arg(221). When substituted with a phenol, the small inhibitor induces the closed conformation of the protein and displaces all waters in the catalytic pocket. Saturated IZD-containing peptides are more potent inhibitors than unsaturated analogs because the IZD heterocycle and phenyl ring directly attached to it bind in a nearly orthogonal orientation with respect to each other, a conformation that is close to the energy minimum of the saturated IZD-phenyl moiety. These results explain why the heterocycle is a potent phosphonate mimetic and an ideal starting point for designing small nonpeptidic inhibitors. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176885 176885]], Insulin resistance, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176885 176885]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Wynn, R.]] | [[Category: Wynn, R.]] | ||
[[Category: Yue, E W.]] | [[Category: Yue, E W.]] | ||
| - | [[Category: MPD]] | ||
[[Category: acetylation]] | [[Category: acetylation]] | ||
[[Category: endoplasmic reticulum]] | [[Category: endoplasmic reticulum]] | ||
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[[Category: protein phosphatase]] | [[Category: protein phosphatase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:23:22 2008'' |
Revision as of 23:23, 30 March 2008
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| , resolution 1.5Å | |||||||
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| Sites: | |||||||
| Ligands: | |||||||
| Activity: | Protein-tyrosine-phosphatase, with EC number 3.1.3.48 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B (P212121)
Overview
Crystal structures of protein-tyrosine phosphatase 1B in complex with compounds bearing a novel isothiazolidinone (IZD) heterocyclic phosphonate mimetic reveal that the heterocycle is highly complementary to the catalytic pocket of the protein. The heterocycle participates in an extensive network of hydrogen bonds with the backbone of the phosphate-binding loop, Phe(182) of the flap, and the side chain of Arg(221). When substituted with a phenol, the small inhibitor induces the closed conformation of the protein and displaces all waters in the catalytic pocket. Saturated IZD-containing peptides are more potent inhibitors than unsaturated analogs because the IZD heterocycle and phenyl ring directly attached to it bind in a nearly orthogonal orientation with respect to each other, a conformation that is close to the energy minimum of the saturated IZD-phenyl moiety. These results explain why the heterocycle is a potent phosphonate mimetic and an ideal starting point for designing small nonpeptidic inhibitors.
About this Structure
2CM2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for inhibition of protein-tyrosine phosphatase 1B by isothiazolidinone heterocyclic phosphonate mimetics., Ala PJ, Gonneville L, Hillman MC, Becker-Pasha M, Wei M, Reid BG, Klabe R, Yue EW, Wayland B, Douty B, Polam P, Wasserman Z, Bower M, Combs AP, Burn TC, Hollis GF, Wynn R, J Biol Chem. 2006 Oct 27;281(43):32784-95. Epub 2006 Aug 17. PMID:16916797
Page seeded by OCA on Mon Mar 31 02:23:22 2008
Categories: Homo sapiens | Protein-tyrosine-phosphatase | Single protein | Ala, P J. | Becker-Pasha, M. | Bower, M. | Burn, T C. | Combs, A P. | Douty, B. | Gonneville, L. | Hillman, M C. | Hollis, G F. | Klabe, R. | Polam, P. | Reid, B G. | Wasserman, Z. | Wayland, B. | Wei, M. | Wynn, R. | Yue, E W. | Acetylation | Endoplasmic reticulum | Hydrolase | Oxidation | Phosphatase | Phosphorylation | Polymorphism | Protein phosphatase
