4gs0: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[ | ==Crystal structure of SHP1 catalytic domain with JAK1 activation loop peptide== | ||
<StructureSection load='4gs0' size='340' side='right' caption='[[4gs0]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4gs0]] is a 3 chain structure with 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=4GS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GS0 FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=FTY:DEOXY-DIFLUOROMETHELENE-PHOSPHOTYROSINE'>FTY</scene>, <scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HCP, PTP1C, PTPN6, SHP-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gs0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gs0 RCSB], [http://www.ebi.ac.uk/pdbsum/4gs0 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
SHP-1 (PTPN6) is a member of the SHP sub-family of protein tyrosine phosphatases and plays a critical role in the regulation of the JAK/STAT signaling pathway. Previous studies suggested that SHP-1 contains a PTP1B-like second phosphotyrosine pocket that allows for binding of tandem phosphotyrosine residues, such as those found in the activation loop of JAK kinases. To discover the structural nature of the interaction between SHP-1 and the JAK family member, JAK1, we determined the 1.8A co-crystal structure of the SHP-1 catalytic domain and a JAK1-derived substrate peptide. This structure reveals electron density for only one bound phosphotyrosine residue. To investigate the role of the predicted second site pocket we determined the structures of SHP-1 in complex with phosphate and sulfate to 1.37A and 1.7A, respectively, and performed anomalous scattering experiments for a selenate-soaked crystal. These crystallographic data suggest that SHP-1 does not contain a PTP1B-like second site pocket. This conclusion is further supported by analysis of the relative dephosphorylation and binding affinities of mono- and tandem-phosphorylated peptide substrates. The crystal structures instead indicate that SHP-1 contains an extended C-terminal helix alpha2' incompatible with the predicted second phosphotyrosine binding site. This study suggests that SHP-1 defines a new category of PTP1B-like protein tyrosine phosphatases with a hindered second phosphotyrosine pocket. | |||
Structure-guided studies of the SHP-1/JAK1 interaction provide new insights into phosphatase catalytic domain substrate recognition.,Alicea-Velazquez NL, Jakoncic J, Boggon TJ J Struct Biol. 2013 Jan 4. pii: S1047-8477(12)00343-7. doi:, 10.1016/j.jsb.2012.12.009. PMID:23296072<ref>PMID:23296072</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | |||
*[[Tyrosine phosphatase|Tyrosine phosphatase]] | |||
== | == References == | ||
[[ | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein-tyrosine-phosphatase]] | [[Category: Protein-tyrosine-phosphatase]] | ||
[[Category: Alicea-Velazquez, N L | [[Category: Alicea-Velazquez, N L]] | ||
[[Category: Boggon, T J | [[Category: Boggon, T J]] | ||
[[Category: Jakoncic, J | [[Category: Jakoncic, J]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Hydrolase-transferase complex]] | [[Category: Hydrolase-transferase complex]] | ||
[[Category: Phosphatase domain]] | [[Category: Phosphatase domain]] | ||
[[Category: Protein-protein complex]] | [[Category: Protein-protein complex]] | ||