View source for 5lso


==Crystal structure of SPF45 UHM domain with cyclic peptide inhibitor==
<StructureSection load='5lso' size='340' side='right'caption='[[5lso]], [[Resolution|resolution]] 2.22&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5lso]] is a 4 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=5LSO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LSO 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]] 2.22&#8491;</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=5lso FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lso OCA], [https://pdbe.org/5lso PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lso RCSB], [https://www.ebi.ac.uk/pdbsum/5lso PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lso ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPF45_HUMAN SPF45_HUMAN] Splice factor that binds to the single stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites. Promotes the utilization of a cryptic splice site created by the beta-110 mutation in the HBB gene. The resulting frameshift leads to sickle cell anemia.<ref>PMID:12015979</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
U2AF homology motifs (UHMs) are atypical RNA Recognition Motif (RRM) domains that mediate critical protein-protein interactions during the regulation of alternative pre-mRNA splicing and other processes. The recognition of UHM domains by UHM Ligand Motif (ULM) peptide sequences plays important roles during early steps of spliceosome assembly. Splicing factor 45 kDa (SPF45) is an alternative splicing factor implicated in breast and lung cancer and splicing regulation of apoptosis-linked pre-mRNAs by SPF45 was shown to depend on interactions of its UHM domain with ULM motifs in constitutive splicing factors. We have developed cyclic peptide inhibitors that target UHM domains. By screening a focused library of linear and cyclic peptides and performing structure-activity relationship (SAR) analysis, we designed cyclic peptides with 4-fold improved binding affinity for the SPF45 UHM domain compared to native ULM ligands and 270-fold selectivity to discriminate UHM domains from alternative and constitutive splicing factors. These inhibitors are useful tools to modulate and dissect mechanisms of alternative splicing regulation.

Rational design of cyclic peptide inhibitors of U2AF homology motif (UHM) domains to modulate pre-mRNA splicing.,Jagtap PK, Garg D, Kapp TG, Will CL, Demmer O, Luhrmann R, Kessler H, Sattler M J Med Chem. 2016 Oct 18. PMID:27753493<ref>PMID:27753493</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5lso" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Garg D]]
[[Category: Jagtap PKA]]
[[Category: Sattler M]]