1g1g: Difference between revisions

Revision as of 17:00, 2 May 2008

CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH A MONO-PHOSPHORYLATED PEPTIDE (ETDY(PTR)RKGGKGLL) FROM THE INSULIN RECEPTOR KINASE

OverviewOverview

The protein tyrosine phosphatase PTP1B is responsible for negatively regulating insulin signaling by dephosphorylating the phosphotyrosine residues of the insulin receptor kinase (IRK) activation segment. Here, by integrating crystallographic, kinetic, and PTP1B peptide binding studies, we define the molecular specificity of this reaction. Extensive interactions are formed between PTP1B and the IRK sequence encompassing the tandem pTyr residues at 1162 and 1163 such that pTyr-1162 is selected at the catalytic site and pTyr-1163 is located within an adjacent pTyr recognition site. This selectivity is attributed to the 70-fold greater affinity for tandem pTyr-containing peptides relative to mono-pTyr peptides and predicts a hierarchical dephosphorylation process. Many elements of the PTP1B-IRK interaction are unique to PTP1B, indicating that it may be feasible to generate specific, small molecule inhibitors of this interaction to treat diabetes and obesity.

About this StructureAbout this Structure

1G1G is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B., Salmeen A, Andersen JN, Myers MP, Tonks NK, Barford D, Mol Cell. 2000 Dec;6(6):1401-12. PMID:11163213 Page seeded by OCA on Fri May 2 17:00:49 2008

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OCA

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 [[Image:1g1g.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_1g1g", creates the "Structure Box" on the page.
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-|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>
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-}}
 '''CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH A MONO-PHOSPHORYLATED PEPTIDE (ETDY(PTR)RKGGKGLL) FROM THE INSULIN RECEPTOR KINASE'''
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 [[Category: Salmeen, A.]]
 [[Category: Tonks, N K.]]
-[[Category: hydrolase (phosphorylation)]]
+[[Category: Peptide complex]]
-[[Category: peptide complex]]
+[[Category: Tyrosine phosphatase]]
-[[Category: tyrosine phosphatase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 17:00:49 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:34:34 2008''