1a5y
From Proteopedia
(New page: 200px<br /> <applet load="1a5y" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a5y, resolution 2.5Å" /> '''PROTEIN TYROSINE PHO...) |
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| - | [[Image:1a5y.gif|left|200px]]<br /> | + | [[Image:1a5y.gif|left|200px]]<br /><applet load="1a5y" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1a5y" size=" | + | |
caption="1a5y, resolution 2.5Å" /> | caption="1a5y, resolution 2.5Å" /> | ||
'''PROTEIN TYROSINE PHOSPHATASE 1B CYSTEINYL-PHOSPHATE INTERMEDIATE'''<br /> | '''PROTEIN TYROSINE PHOSPHATASE 1B CYSTEINYL-PHOSPHATE INTERMEDIATE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Protein-tyrosine phosphatases (PTPs) are signal transduction enzymes that | + | Protein-tyrosine phosphatases (PTPs) are signal transduction enzymes that catalyze the dephosphorylation of phosphotyrosine residues via the formation of a transient cysteinyl-phosphate intermediate. The mechanism of hydrolysis of this intermediate has been examined by generating a Gln-262 --> Ala mutant of PTP1B, which allows the accumulation and trapping of the intermediate within a PTP1B crystal. The structure of the intermediate at 2.5-A resolution reveals that a conformationally flexible loop (the WPD loop) is closed over the entrance to the catalytic site, sequestering the phosphocysteine intermediate and catalytic site water molecules and preventing nonspecific phosphoryltransfer reactions to extraneous phosphoryl acceptors. One of the catalytic site water molecules, the likely nucleophile, forms a hydrogen bond to the putative catalytic base, Asp-181. In the wild-type enzyme, the nucleophilic water molecule would be coordinated by the side chain of Gln-262. In combination with our previous structural data, we can now visualize each of the reaction steps of the PTP catalytic pathway. The hydrolysis of the cysteinyl-phosphate intermediate of PTPs is reminiscent of GTP hydrolysis by the GTPases, in that both families of enzymes utilize an invariant Gln residue to coordinate the attacking nucleophilic water molecule. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1A5Y 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:// | + | 1A5Y 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=1A5Y OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Barford, D.]] | [[Category: Barford, D.]] | ||
| - | [[Category: Flint, A | + | [[Category: Flint, A J.]] |
| - | [[Category: Pannifer, A | + | [[Category: Pannifer, A D.P.]] |
| - | [[Category: Tonks, N | + | [[Category: Tonks, N K.]] |
[[Category: dephosphorylation]] | [[Category: dephosphorylation]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:41:14 2008'' |
Revision as of 09:41, 21 February 2008
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PROTEIN TYROSINE PHOSPHATASE 1B CYSTEINYL-PHOSPHATE INTERMEDIATE
Contents |
Overview
Protein-tyrosine phosphatases (PTPs) are signal transduction enzymes that catalyze the dephosphorylation of phosphotyrosine residues via the formation of a transient cysteinyl-phosphate intermediate. The mechanism of hydrolysis of this intermediate has been examined by generating a Gln-262 --> Ala mutant of PTP1B, which allows the accumulation and trapping of the intermediate within a PTP1B crystal. The structure of the intermediate at 2.5-A resolution reveals that a conformationally flexible loop (the WPD loop) is closed over the entrance to the catalytic site, sequestering the phosphocysteine intermediate and catalytic site water molecules and preventing nonspecific phosphoryltransfer reactions to extraneous phosphoryl acceptors. One of the catalytic site water molecules, the likely nucleophile, forms a hydrogen bond to the putative catalytic base, Asp-181. In the wild-type enzyme, the nucleophilic water molecule would be coordinated by the side chain of Gln-262. In combination with our previous structural data, we can now visualize each of the reaction steps of the PTP catalytic pathway. The hydrolysis of the cysteinyl-phosphate intermediate of PTPs is reminiscent of GTP hydrolysis by the GTPases, in that both families of enzymes utilize an invariant Gln residue to coordinate the attacking nucleophilic water molecule.
Disease
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]
About this Structure
1A5Y 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.
Reference
Visualization of the cysteinyl-phosphate intermediate of a protein-tyrosine phosphatase by x-ray crystallography., Pannifer AD, Flint AJ, Tonks NK, Barford D, J Biol Chem. 1998 Apr 24;273(17):10454-62. PMID:9553104
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