2cm2: Difference between revisions
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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. | ||
==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: 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'' | ||
