View source for 5xn3


==Crystal structure of SPSB2 in complex with a rational designed RGD containing cyclic peptide inhibitor of SPSB2-iNOS interaction==
<StructureSection load='5xn3' size='340' side='right'caption='[[5xn3]], [[Resolution|resolution]] 1.34&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5xn3]] is a 2 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=5XN3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XN3 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]] 1.34&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PRD_002275:cR8+peptide+from+NOS2'>PRD_002275</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=5xn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xn3 OCA], [https://pdbe.org/5xn3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xn3 RCSB], [https://www.ebi.ac.uk/pdbsum/5xn3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xn3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPSB2_HUMAN SPSB2_HUMAN] Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.<ref>PMID:15601820</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
SPRY domain-containing SOCS box protein 2 (SPSB2) is a negative regulator of inducible nitric oxide synthase (iNOS) that modulates the lifetime of iNOS and thus the levels of nitric oxide (NO) production. Inhibitors that can disrupt the endogenous SPSB2-iNOS interaction and augment NO production have potential as novel antimicrobial and anticancer drugs. In this study, we have designed a cyclic peptide (cR8), containing an RGD motif and the SPSB2 binding motif (DINNNV). ITC and chemical shift perturbation showed that cR8 binds to the iNOS binding site on SPSB2 with a Kd of 671 nM, and saturation transfer difference NMR showed that cR8 binds to alphavbeta3 integrin-expressing cells. Moreover, we determined the crystal structure of SPSB2 in complex with cR8, at a resolution of 1.34 A. cR8 forms extensive hydrogen bonding with SPSB2 residues, but loss of an intramolecular hydrogen bond that is present in SPSB2-bound iNOS peptide may destabilize the bound conformation of cR8 and lead to a gentle reduction in SPSB2 binding affinity. These results serve as a useful basis for designing site-directed SPSB2 inhibitors in the future.

Crystal structure of SPSB2 in complex with a rational designed RGD-containing cyclic peptide inhibitor of SPSB2-iNOS interaction.,You T, Wang Y, Li K, Zhang D, Wei H, Luo Y, Li H, Lu Y, Su X, Kuang Z Biochem Biophys Res Commun. 2017 Jul 29;489(3):346-352. doi:, 10.1016/j.bbrc.2017.05.122. Epub 2017 May 24. PMID:28549582<ref>PMID:28549582</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5xn3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kuang Z]]
[[Category: You T]]