Crystal structure of the SPRY domain of human SPSB2 in the apo state
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 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.
This report continues the development of ALIs as a clinical tool in wildlife while systematically testing one possible method for determining an optimal ALI for a particular species. PMID: 32228119 [PubMed - as supplied by publisher]
Authors: Park J, Kim J, Chen Y, Song HC, Chen Y, Zheng M, Surh YJ, Kim UH, Park JW, Joe Y, Chung HT Abstract Oxidative stress is recognised as a key factor that can lead to cellular senescence and aging. Carbon monoxide (CO) is produced by haemoxygenase-1 (HO-1), which exerts cytoprotective effects in aging-related diseases, whereas the effect of CO on cellular senescence and aging has not been elucidated. In the current study, we clearly demonstrated that CO delays the process of cellular senescence and aging through regulation of miR-34a and Sirt1 expression. CO reduced H2O2-induced premature senescence in human ...
Publication date: Available online 1 April 2020Source: Journal of Microbiological MethodsAuthor(s): Wisnu Tafroji, Felicia Monica Bernadette, Ernawati A. Giri Rachman, Dodi Safari
Publication date: Available online 2 April 2020Source: Journal of Microbiology, Immunology and InfectionAuthor(s): Chun-Min Kang, Xiang-Jun Chen, Ching-Chin Chih, Chen-Ching Hsu, Ping-Hung Chen, Tai fen Lee, Lee-Jene Teng, Po-Ren Hsueh
Publication date: Available online 1 April 2020Source: Journal of Microbiology, Immunology and InfectionAuthor(s): Chien-Yu Lee, Pi-Sheng Wang, Yuan-Der Huang, Yung-Ching Lin, Yung-Nien Hsu, Shih-Chung Chen
Publication date: Available online 1 April 2020Source: Journal of Microbiology, Immunology and InfectionAuthor(s): Chia-Hung Liao, Shih-Chang Hung, Yuan-Ti Lee, Hung-Chang Hung, Po-Ren Hsueh
Publication date: Available online 2 April 2020Source: Statistics &Probability LettersAuthor(s): Junhao Guo, Jie Zhou, Sanfeng Hu
Publication date: Available online 1 April 2020Source: Statistics &Probability LettersAuthor(s): S. Mousavinasr, C.R. Gonçalves, C.C.Y. Dorea
Publication date: 1 May 2020Source: Sensors and Actuators A: Physical, Volume 306Author(s): Chuang Ge, Leixiang Bian, Jiayang Li, Mingyou Zhong, Songtong Han, Yunfei Jia
Publication date: Available online 1 April 2020Source: Results in PhysicsAuthor(s): U.S. Okorie, A.N. Ikot, E.O. Chukwuocha, G.J. Rampho
More News: Biochemistry