2cm7: Difference between revisions
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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 .. | 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== | ==About this Structure== | ||
2CM7 is a | 2CM7 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 IZD as [http://en.wikipedia.org/wiki/ligand ligand]. 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] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CM7 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: protein phosphatase]] | [[Category: protein phosphatase]] | ||
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Revision as of 15:24, 5 November 2007
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STRUCTURAL BASIS FOR INHIBITION OF PROTEIN TYROSINE PHOSPHATASE 1B BY ISOTHIAZOLIDINONE HETEROCYCLIC PHOSPHONATE MIMETICS
OverviewOverview
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 StructureAbout this Structure
2CM7 is a Single protein structure of sequence from Homo sapiens with IZD as ligand. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
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
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- 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.
- IZD
- Acetylation
- Endoplasmic reticulum
- Hydrolase
- Oxidation
- Phosphatase
- Phosphorylation
- Polymorphism
- Protein phosphatase