6c4u: Difference between revisions
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==Engineered FHA with Myc-pTBD peptide== | |||
<StructureSection load='6c4u' size='340' side='right' caption='[[6c4u]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6c4u]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C4U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C4U FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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=6c4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c4u OCA], [http://pdbe.org/6c4u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c4u RCSB], [http://www.ebi.ac.uk/pdbsum/6c4u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c4u ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Transcription factor c-Myc is an oncoprotein that is regulated at the post-translational level through phosphorylation of two conserved residues, Serine 62 (Ser62) and Threonine 58 (Thr58). A highly specific tool capable of recognizing Myc via pThr58 is needed to monitor activation and localization. Through phage display, we have isolated 10 engineered Forkhead-associated (FHA) domains that selectively bind to a phosphothreonine (pThr)-containing peptide (53-FELLPpTPPLSPS-64) segment of human c-Myc. One domain variant was observed to bind to the Myc-pThr58 peptide with a KD value of 800nM and had >1,000-fold discrimination between the phosphorylated and non-phosphorylated peptide. The crystal structure of the engineered FHA Myc-pThr-binding domain (Myc-pTBD) was solved in complex with its cognate ligand. The Myc-pTBD was observed to be structurally similar to the yeast Rad9 FHA1 domain, except that its beta4-beta5 and beta10-beta11 loops form a hydrophobic pocket to facilitate the interaction between the domain and the peptide ligand. The Myc-pTBD's specificity for its cognate ligand was demonstrated to be on a par with 3 commercial polyclonal antibodies, suggesting that this recombinant reagent is a viable alternative to antibodies for monitoring Myc regulation. | |||
Generating a recombinant phosphothreonine-binding domain for a phosphopeptide of the human transcription factor, c-Myc.,Venegas LA, Kall SL, Bankole O, Lavie A, Kay B N Biotechnol. 2018 May 12. pii: S1871-6784(18)30120-1. doi:, 10.1016/j.nbt.2018.05.001. PMID:29763736<ref>PMID:29763736</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6c4u" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Kall, S L]] | |||
[[Category: Lavie, A]] | [[Category: Lavie, A]] | ||
[[Category: | [[Category: Fha]] | ||
[[Category: Myc pt58 target]] | |||
[[Category: Peptide binding protein]] | |||
[[Category: Protein engineering]] | |||
Revision as of 05:33, 30 May 2018
Engineered FHA with Myc-pTBD peptide
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