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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.