View source for 6fmk


==pVHL:EloB:EloC in complex with N-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamothioyl) pyrrolidin-1-yl)-1-thioxopropan-2-yl)acetamide (ligand 4)==
<StructureSection load='6fmk' size='340' side='right'caption='[[6fmk]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fmk]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FMK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FMK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=DV8:~{N}-[(2~{S})-1-[(2~{S},4~{R})-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamothioyl]-4-oxidanyl-pyrrolidin-1-yl]-1-sulfanylidene-propan-2-yl]ethanamide'>DV8</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6fmk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fmk OCA], [https://pdbe.org/6fmk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fmk RCSB], [https://www.ebi.ac.uk/pdbsum/6fmk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fmk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ELOB_HUMAN ELOB_HUMAN] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:7638163</ref> <ref>PMID:15590694</ref>   The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Thioamide substitution influences hydrogen bond and n --&gt; pi( *) interactions involved in the conformational stability of protein secondary structures and oligopeptides. Hydroxyproline is the key recognition element of small molecules targeting the von Hippel-Lindau (VHL) E3 ligase, which are of interest as probes of hypoxia signaling and ligands for PROTAC conjugation. We hypothesized that VHL ligands could be a privileged model system to evaluate the contribution of these interactions to protein:ligand complex formation. Herein we report the synthesis of VHL ligands bearing thioamide substitutions at the central hydroxyproline moiety, and characterize their binding by fluorescence polarization, isothermal titration calorimetry, X-ray crystallography and molecular modeling. In spite of a conserved binding mode, the substitution pattern had a pronounced impact on the ligand affinities. Together the results underscore the role of hydrogen bond and n --&gt; pi( *) interactions in fine tuning hydroxyproline recognition by VHL.

Thioamide substitution to probe the hydroxyproline recognition of VHL ligands.,Soares P, Lucas X, Ciulli A Bioorg Med Chem. 2018 Mar 23. pii: S0968-0896(18)30348-1. doi:, 10.1016/j.bmc.2018.03.034. PMID:29650462<ref>PMID:29650462</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fmk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Elongation factor 3D structures|Elongation factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ciulli A]]
[[Category: Lucas X]]
[[Category: Soares P]]