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5xn3

From Proteopedia

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Current revision

Crystal structure of SPSB2 in complex with a rational designed RGD containing cyclic peptide inhibitor of SPSB2-iNOS interaction

Structural highlights

5xn3 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.34Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kamura T, Maenaka K, Kotoshiba S, Matsumoto M, Kohda D, Conaway RC, Conaway JW, Nakayama KI. VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes Dev. 2004 Dec 15;18(24):3055-65. PMID:15601820 doi:http://dx.doi.org/10.1101/gad.1252404
↑ You T, Wang Y, Li K, Zhang D, Wei H, Luo Y, Li H, Lu Y, Su X, Kuang Z. Crystal structure of SPSB2 in complex with a rational designed RGD-containing cyclic peptide inhibitor of SPSB2-iNOS interaction. 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 doi:http://dx.doi.org/10.1016/j.bbrc.2017.05.122

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5xn3"

Categories: Homo sapiens | Large Structures | Kuang Z | You T

@@ Line 1: / Line 1: @@
 ==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=''>
+<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 [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XN3 FirstGlance]. <br>
+<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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPSB2, GRCC9, SSB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</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='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=5xn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xn3 OCA], [http://pdbe.org/5xn3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xn3 RCSB], [http://www.ebi.ac.uk/pdbsum/5xn3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xn3 ProSAT]</span></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 ==
-[[http://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>
+[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 ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Kuang, Z]]
+[[Category: Large Structures]]
-[[Category: You, T]]
+[[Category: Kuang Z]]
-[[Category: Cyclic peptide inhibitor]]
+[[Category: You T]]
-[[Category: E3 ubiquitin]]
-[[Category: Inducible nitric oxide synthase]]
-[[Category: Ligase]]
-[[Category: Nitric oxide]]
-[[Category: Protein binding-inhibitor complex]]
-[[Category: Socs box protein]]
-[[Category: Spry domain-containing]]

5xn3

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Current revision

Crystal structure of SPSB2 in complex with a rational designed RGD containing cyclic peptide inhibitor of SPSB2-iNOS interaction

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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