Two high‐resolution structures of the human E3 ubiquitin ligase Siah1. Issue 12 (1st December 2013)

• Record Type: Journal Article
• Authors: Rimsa, Vadim; Eadsforth, Thomas C.; Hunter, William N.
• Is Part Of: Acta crystallographica. Volume 69:Issue 12(2013:Dec.)
• Page Start: 1339
• Page End: 1343
• Publication Date: 2013-12-01
• Subjects: Crystallography -- Periodicals; Crystals -- Periodicals; 548
• DOI: 10.1107/S1744309113031448
• Languages: English
• ISSNs: 1744-3091

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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.</p> </abstract>