3qht

<StructureSection load='3qht' size='340' side='right' caption='[[3qht]], [[Resolution|resolution]] 2.40&Aring;' scene=''>

<table><tr><td colspan='2'>[[3qht]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QHT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QHT 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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SMT3, YDR510W, D9719.15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</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=3qht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qht OCA], [http://pdbe.org/3qht PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qht RCSB], [http://www.ebi.ac.uk/pdbsum/3qht PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qht ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/SMT3_YEAST SMT3_YEAST]] Not known; suppressor of MIF2 mutations.

Discriminating closely related molecules remains a major challenge in the engineering of binding proteins and inhibitors. Here we report the development of highly selective inhibitors of small ubiquitin-related modifier (SUMO) family proteins. SUMOylation is involved in the regulation of diverse cellular processes. Functional differences between two major SUMO isoforms in humans, SUMO1 and SUMO2/3, are thought to arise from distinct interactions mediated by each isoform with other proteins containing SUMO-interacting motifs (SIMs). However, the roles of such isoform-specific interactions are largely uncharacterized due in part to the difficulty in generating high-affinity, isoform-specific inhibitors of SUMO/SIM interactions. We first determined the crystal structure of a "monobody," a designed binding protein based on the fibronectin type III scaffold, bound to the yeast homolog of SUMO. This structure illustrated a mechanism by which monobodies bind to the highly conserved SIM-binding site while discriminating individual SUMO isoforms. Based on this structure, we designed a SUMO-targeted library from which we obtained monobodies that bound to the SIM-binding site of human SUMO1 with K(d) values of approximately 100 nM but bound to SUMO2 400 times more weakly. The monobodies inhibited SUMO1/SIM interactions and, unexpectedly, also inhibited SUMO1 conjugation. These high-affinity and isoform-specific inhibitors will enhance mechanistic and cellular investigations of SUMO biology.

 

== References ==

[[Category: Atcc 18824]]

[[Category: Synthetic construct sequences]]

[[Category: Gilbreth, R N]]

[[Category: Koide, S]]

[[Category: De novo protein]]

[[Category: Yeast small ubiquitin-like modifier]]