6JKJ

Crystal structure of human SPSB2 in the apo-state

Summary for 6JKJ

• Entry DOI: 10.2210/pdb6jkj/pdb
• Descriptor: SPRY domain-containing SOCS box protein 2 (2 entities in total)
• Functional Keywords: e3 ubiquitin ligase, spry domain-containing socs box protein, spsb2, protein binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 45793.21

Authors

Luo, Y.,Kuang, Z. (deposition date: 2019-03-01, release date: 2019-07-03, Last modification date: 2023-11-22)

Primary citation

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.,Sect.F, 75:412-418, 2019

PubMed Abstract: 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 Å. 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 His 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.

PubMed: 31204687
DOI: 10.1107/S2053230X1900623X

Experimental method

X-RAY DIFFRACTION (1.9 Å)