1aax: Difference between revisions
New page: left|200px<br /> <applet load="1aax" size="450" color="white" frame="true" align="right" spinBox="true" caption="1aax, resolution 1.9Å" /> '''CRYSTAL STRUCTURE OF... |
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'''CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH TWO BIS(PARA-PHOSPHOPHENYL)METHANE (BPPM) MOLECULES'''<br /> | '''CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH TWO BIS(PARA-PHOSPHOPHENYL)METHANE (BPPM) MOLECULES'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1AAX 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 MG and BPM as [http://en.wikipedia.org/wiki/ligands ligands]. 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] Full crystallographic information is available from [http:// | 1AAX 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 <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=BPM:'>BPM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AAX OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: phosphorylation]] | [[Category: phosphorylation]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:28:32 2008'' | ||
Revision as of 16:28, 15 February 2008
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CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH TWO BIS(PARA-PHOSPHOPHENYL)METHANE (BPPM) MOLECULES
OverviewOverview
The structure of the catalytically inactive mutant (C215S) of the human, protein-tyrosine phosphatase 1B (PTP1B) has been solved to high resolution, in two complexes. In the first, crystals were grown in the presence of, bis-(para-phosphophenyl) methane (BPPM), a synthetic high-affinity, low-molecular weight nonpeptidic substrate (Km = 16 microM), and the, structure was refined to an R-factor of 18. 2% at 1.9 A resolution. In the, second, crystals were grown in a saturating concentration of, phosphotyrosine (pTyr), and the structure was refined to an R-factor of, 18.1% at 1.85 A. Difference Fourier maps showed that BPPM binds PTP1B in, two mutually exclusive modes, one in which it occupies the canonical, pTyr-binding site (the active site), and another in which a phosphophenyl, moiety interacts with a set of residues not previously observed to bind, aryl phosphates. The identification of a second pTyr molecule at the same, site in the PTP1B/C215S-pTyr complex confirms that these residues, constitute a low-affinity noncatalytic aryl phosphate-binding site., Identification of a second aryl phosphate binding site adjacent to the, active site provides a paradigm for the design of tight-binding, highly, specific PTP1B inhibitors that can span both the active site and the, adjacent noncatalytic site. This design can be achieved by tethering, together two small ligands that are individually targeted to the active, site and the proximal noncatalytic site.
DiseaseDisease
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]
About this StructureAbout this Structure
1AAX is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.
ReferenceReference
Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase 1B: a paradigm for inhibitor design., Puius YA, Zhao Y, Sullivan M, Lawrence DS, Almo SC, Zhang ZY, Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13420-5. PMID:9391040
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