1g1f: Difference between revisions
New page: left|200px<br /> <applet load="1g1f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g1f, resolution 2.0Å" /> '''CRYSTAL STRUCTURE OF... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1g1f.gif|left|200px]]<br /> | [[Image:1g1f.gif|left|200px]]<br /><applet load="1g1f" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1g1f" size=" | |||
caption="1g1f, resolution 2.0Å" /> | caption="1g1f, resolution 2.0Å" /> | ||
'''CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH A TRI-PHOSPHORYLATED PEPTIDE (RDI(PTR)ETD(PTR)(PTR)RK) FROM THE INSULIN RECEPTOR KINASE'''<br /> | '''CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH A TRI-PHOSPHORYLATED PEPTIDE (RDI(PTR)ETD(PTR)(PTR)RK) FROM THE INSULIN RECEPTOR KINASE'''<br /> | ||
==Overview== | ==Overview== | ||
The protein tyrosine phosphatase PTP1B is responsible for negatively | 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. | ||
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
1G1F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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:// | 1G1F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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=1G1F OCA]. | ||
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: Protein-tyrosine-phosphatase]] | [[Category: Protein-tyrosine-phosphatase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Andersen, J | [[Category: Andersen, J N.]] | ||
[[Category: Barford, D.]] | [[Category: Barford, D.]] | ||
[[Category: Myers, M | [[Category: Myers, M P.]] | ||
[[Category: Salmeen, A.]] | [[Category: Salmeen, A.]] | ||
[[Category: Tonks, N | [[Category: Tonks, N K.]] | ||
[[Category: hydrolase (phosphorylation)]] | [[Category: hydrolase (phosphorylation)]] | ||
[[Category: peptide complex]] | [[Category: peptide complex]] | ||
[[Category: tyrosine phosphatase]] | [[Category: tyrosine phosphatase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:44:56 2008'' | ||
Revision as of 13:45, 21 February 2008
|
CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH A TRI-PHOSPHORYLATED PEPTIDE (RDI(PTR)ETD(PTR)(PTR)RK) 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.
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
1G1F is a Single protein structure of sequence from Homo sapiens. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 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 Thu Feb 21 12:44:56 2008