2cm2: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
==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== | ||
2CM2 is a | 2CM2 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 MPD 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=2CM2 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 42: | Line 42: | ||
[[Category: protein phosphatase]] | [[Category: protein phosphatase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:29:31 2007'' | ||
