5xn3: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 5xn3 is ~~ON HOLD~~

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

== 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>

</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>

<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>

</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>

== 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.

~~Authors:~~ You, T., Kuang, Z.

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>

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

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

[[Category: ~~Unreleased Structures~~]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Human]]

[[Category: Kuang, Z]]

[[Category: You, T]]

[[Category: Cyclic peptide inhibitor]]

[[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]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5xn3 is ON HOLD
+==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 [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>
+</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>
+<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>
+</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>
+<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.
-Authors: You, T., Kuang, Z.
+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>
-Description: Crystal structure of SPSB2 in complex with a rational designed RGD containing cyclic peptide inhibitor of SPSB2-iNOS interaction
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5xn3" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human]]
 [[Category: Kuang, Z]]
 [[Category: You, T]]
+[[Category: Cyclic peptide inhibitor]]
+[[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]]