1i57: Difference between revisions
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[[Image:1i57.gif|left|200px]] | [[Image:1i57.gif|left|200px]] | ||
'''CRYSTAL STRUCTURE OF APO HUMAN PTP1B (C215S) MUTANT''' | {{Structure | ||
|PDB= 1i57 |SIZE=350|CAPTION= <scene name='initialview01'>1i57</scene>, resolution 2.1Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=CL:CHLORIDE ION'>CL</scene> | |||
|ACTIVITY= [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] | |||
|GENE= PTN1_HUMAN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''CRYSTAL STRUCTURE OF APO HUMAN PTP1B (C215S) MUTANT''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1I57 is a [ | 1I57 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I57 OCA]. | ||
==Reference== | ==Reference== | ||
The structure of apo protein-tyrosine phosphatase 1B C215S mutant: more than just an S --> O change., Scapin G, Patel S, Patel V, Kennedy B, Asante-Appiah E, Protein Sci. 2001 Aug;10(8):1596-605. PMID:[http:// | The structure of apo protein-tyrosine phosphatase 1B C215S mutant: more than just an S --> O change., Scapin G, Patel S, Patel V, Kennedy B, Asante-Appiah E, Protein Sci. 2001 Aug;10(8):1596-605. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11468356 11468356] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein-tyrosine-phosphatase]] | [[Category: Protein-tyrosine-phosphatase]] | ||
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[[Category: wpd loop]] | [[Category: wpd loop]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:45:42 2008'' | ||
Revision as of 12:45, 20 March 2008
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| , resolution 2.1Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | PTN1_HUMAN (Homo sapiens) | ||||||
| Activity: | Protein-tyrosine-phosphatase, with EC number 3.1.3.48 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF APO HUMAN PTP1B (C215S) MUTANT
OverviewOverview
Protein-tyrosine phosphatases catalyze the hydrolysis of phosphate monoesters via a two-step mechanism involving a covalent phospho-enzyme intermediate. Biochemical and site-directed mutagenesis experiments show that the invariant Cys residue present in the PTPase signature motif (H/V)CX(5)R(S/T) (i.e., C215 in PTP1B) is absolutely required for activity. Mutation of the invariant Cys to Ser results in a catalytically inactive enzyme, which still is capable of binding substrates and inhibitors. Although it often is assumed that substrate-trapping mutants such as the C215S retain, in solution, the structural and binding properties of wild-type PTPases, significant differences have been found in the few studies that have addressed this issue, suggesting that the mutation may lead to structural/conformational alterations in or near the PTP1B binding site. Several crystal structures of apo-WT PTP1B, and of WT- and C215S-mutant PTP1B in complex with different ligands are available, but no structure of the apo-PTP1B C215S has ever been reported. In all previously reported structures, residues of the PTPase signature motif have an identical conformation, while residues of the WPD loop (a surface loop which includes the catalytic Asp) assume a different conformation in the presence or absence of ligand. These observations led to the hypothesis that the different spectroscopic and thermodynamic properties of the mutant protein may be the result of a different conformation for the WPD loop. We report here the structure of the apo-PTP1B C215S mutant, which reveals that, while the WPD loop is in the open conformation observed in the apo WT enzyme crystal structure, the residues of the PTPases signature motif are in a dramatically different conformation. These results provide a structural basis for the differences in spectroscopic properties and thermodynamic parameters in inhibitor binding observed for the wild-type and mutant enzymes.
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
1I57 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The structure of apo protein-tyrosine phosphatase 1B C215S mutant: more than just an S --> O change., Scapin G, Patel S, Patel V, Kennedy B, Asante-Appiah E, Protein Sci. 2001 Aug;10(8):1596-605. PMID:11468356
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