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{{STRUCTURE_4ca1|  PDB=4ca1  |  SCENE=  }}
==Crystal structure of Siah1 at 1.58 A resolution.==
===Crystal structure of Siah1 at 1.58 A resolution.===
<StructureSection load='4ca1' size='340' side='right' caption='[[4ca1]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
{{ABSTRACT_PUBMED_24316825}}
== Structural highlights ==
<table><tr><td colspan='2'>[[4ca1]] 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=4CA1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CA1 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c9z|4c9z]]</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=4ca1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ca1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ca1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ca1 PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Siah1 is an E3 ubiquitin ligase that contributes to proteasome-mediated degradation of multiple targets in key cellular processes and which shows promise as a therapeutic target in oncology. Structures of a truncated Siah1 bound to peptide-based inhibitors have been reported. Here, new crystallization conditions have allowed the determination of a construct encompassing dual zinc-finger subdomains and substrate-binding domains at significantly higher resolution. Although the crystals appear isomorphous, two structures present distinct states in which the spatial orientation of one zinc-finger subdomain differs with respect to the rest of the dimeric protein. Such a difference, which is indicative of conformational freedom, infers potential biological relevance related to recognition of binding partners. The crystallization conditions and improved models of Siah1 may aid future studies investigating Siah1-ligand complexes.


==Function==
Two high-resolution structures of the human E3 ubiquitin ligase Siah1.,Rimsa V, Eadsforth TC, Hunter WN Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Dec;69(Pt 12):1339-43., doi: 10.1107/S1744309113031448. Epub 2013 Nov 28. PMID:24316825<ref>PMID:24316825</ref>
[[http://www.uniprot.org/uniprot/SIAH1_HUMAN SIAH1_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3. Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins.<ref>PMID:9334332</ref> <ref>PMID:9858595</ref> <ref>PMID:11146551</ref> <ref>PMID:10747903</ref> <ref>PMID:11389839</ref> <ref>PMID:11389840</ref> <ref>PMID:11483517</ref> <ref>PMID:11483518</ref> <ref>PMID:11752454</ref> <ref>PMID:12072443</ref> <ref>PMID:14506261</ref> <ref>PMID:14654780</ref> <ref>PMID:14645235</ref> <ref>PMID:15064394</ref> <ref>PMID:18536714</ref> <ref>PMID:19224863</ref> <ref>PMID:20508617</ref> <ref>PMID:22483617</ref> <ref>PMID:16085652</ref>


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4ca1]] 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=4CA1 OCA].
</div>


==Reference==
==See Also==
<ref group="xtra">PMID:024316825</ref><references group="xtra"/><references/>
*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Human]]
[[Category: Eadsforth, T C.]]
[[Category: Eadsforth, T C]]
[[Category: Hunter, W N.]]
[[Category: Hunter, W N]]
[[Category: Rimsa, V.]]
[[Category: Rimsa, V]]
[[Category: Ligase]]
[[Category: Ligase]]

Revision as of 21:07, 21 December 2014

Crystal structure of Siah1 at 1.58 A resolution.Crystal structure of Siah1 at 1.58 A resolution.

Structural highlights

4ca1 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , ,
Resources:FirstGlance, OCA, RCSB, PDBsum

Publication Abstract from PubMed

Siah1 is an E3 ubiquitin ligase that contributes to proteasome-mediated degradation of multiple targets in key cellular processes and which shows promise as a therapeutic target in oncology. Structures of a truncated Siah1 bound to peptide-based inhibitors have been reported. Here, new crystallization conditions have allowed the determination of a construct encompassing dual zinc-finger subdomains and substrate-binding domains at significantly higher resolution. Although the crystals appear isomorphous, two structures present distinct states in which the spatial orientation of one zinc-finger subdomain differs with respect to the rest of the dimeric protein. Such a difference, which is indicative of conformational freedom, infers potential biological relevance related to recognition of binding partners. The crystallization conditions and improved models of Siah1 may aid future studies investigating Siah1-ligand complexes.

Two high-resolution structures of the human E3 ubiquitin ligase Siah1.,Rimsa V, Eadsforth TC, Hunter WN Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Dec;69(Pt 12):1339-43., doi: 10.1107/S1744309113031448. Epub 2013 Nov 28. PMID:24316825[1]

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

See Also

References

  1. ↑ Rimsa V, Eadsforth TC, Hunter WN. Two high-resolution structures of the human E3 ubiquitin ligase Siah1. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Dec;69(Pt 12):1339-43., doi: 10.1107/S1744309113031448. Epub 2013 Nov 28. PMID:24316825 doi:http://dx.doi.org/10.1107/S1744309113031448

4ca1, resolution 1.58Å

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