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| | <StructureSection load='6jkj' size='340' side='right'caption='[[6jkj]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='6jkj' size='340' side='right'caption='[[6jkj]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6jkj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JKJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6jkj]] 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=6JKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JKJ FirstGlance]. <br> |
| - | </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=6jkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jkj OCA], [http://pdbe.org/6jkj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jkj RCSB], [http://www.ebi.ac.uk/pdbsum/6jkj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jkj ProSAT]</span></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]] 1.9Å</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=6jkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jkj OCA], [https://pdbe.org/6jkj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jkj RCSB], [https://www.ebi.ac.uk/pdbsum/6jkj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jkj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kuang, Z]] | + | [[Category: Kuang Z]] |
| - | [[Category: Luo, Y]] | + | [[Category: Luo Y]] |
| - | [[Category: E3 ubiquitin ligase]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Spry domain-containing socs box protein]]
| + | |
| - | [[Category: Spsb2]]
| + | |
| Structural highlights
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
The SPRY domain-containing SOCS box protein 2 (SPSB2) is one of four mammalian SPSB proteins that are characterized by a C-terminal SOCS box and a central SPRY/B30.2 domain. SPSB2 interacts with inducible nitric oxide synthase (iNOS) via the SPRY domain and polyubiquitinates iNOS, resulting in its proteasomal degradation. Inhibitors that can disrupt SPSB2-iNOS interaction and augment NO production may serve as novel anti-infective and anticancer agents. The previously determined murine SPSB2 structure may not reflect the true apo conformation of the iNOS-binding site. Here, the crystal structure of human SPSB2 SPRY domain in the apo state is reported at a resolution of 1.9 A. Comparison of the apo and ligand-bound structures reveals that the iNOS-binding site is highly preformed and that major conformational changes do not occur upon ligand binding. Moreover, the C-terminal His6 tag of the recombinant protein binds to a shallow pocket adjacent to the iNOS-binding site on a crystallographically related SPSB2 molecule. These findings may help in structure-based and fragment-based SPSB2 inhibitor design in the future.
Crystal structure of the SPRY domain of human SPSB2 in the apo state.,Luo Y, Li K, Yang J, Zhang D, Zhou Y, Kuang Z Acta Crystallogr F Struct Biol Commun. 2019 Jun 1;75(Pt 6):412-418. doi:, 10.1107/S2053230X1900623X. Epub 2019 May 10. PMID:31204687[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
- ↑ Luo Y, Li K, Yang J, Zhang D, Zhou Y, Kuang Z. Crystal structure of the SPRY domain of human SPSB2 in the apo state. Acta Crystallogr F Struct Biol Commun. 2019 Jun 1;75(Pt 6):412-418. doi:, 10.1107/S2053230X1900623X. Epub 2019 May 10. PMID:31204687 doi:http://dx.doi.org/10.1107/S2053230X1900623X
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