2cm2: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 6: | Line 6: | ||
==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. | ||
==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== | ||
| Line 42: | Line 45: | ||
[[Category: protein phosphatase]] | [[Category: protein phosphatase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:17:15 2007'' | ||
