Zinc-mediated binding of a low-molecular-weight stabilizer of the host anti-viral factor apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G

Radwan Mohamed O.; Sonoda Sachiko; Ejima TomohikoTanaka AyumiKoga RyokoOkamoto YoshinariFujita MikakoOtsuka Masami

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Zinc-mediated binding of a low-molecular-weight stabilizer of the host anti-viral factor apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G

机译：Zinc-mediated binding of a low-molecular-weight stabilizer of the host anti-viral factor apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G

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Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (APOBEC3G, A3G), is a human anti-virus restriction protein which works deaminase-dependently and - independently. A3G is known to be ubiquitinated by HIV-1 viral infectivity factor (Vif) protein, leading to proteasomal degradation. A3G contains two zinc ions at the N-terminal domain and the C-terminal domain. Four lysine residues, K-297, K-301, K-303, and K-334, are known to be required for Vif-mediated A3G ubiquitination and degradation. Previously, we reported compound SN-1, a zinc chelator that increases steady-state expression level of A3G in the presence of Vif. In this study, we prepared Biotin-SN-1, a biotinylated derivative of SN-1, to study the SN-1-A3G interaction. A pull-down assay revealed that Biotin-SN-1 bound A3G. A zinc-abstraction experiment indicated that SN-1 binds to the zinc site of A3G. We carried out a SN-1-A3G docking study using molecular operating environment. The calculations revealed that SN-1 binds to the C-terminal domain through Zn2+, H-216, P-247, C-288, and Y-315. Notably, SN-1-binding covers the H-257, E-259, C-288, and C-291 residues that participate in zinc-mediated deamination, and the ubiquitination regions of A3G. The binding of SN-1 presumably perturbs the secondary structure between C-288 and Y-315, leading to less efficient ubiquitination. (C) 2016 Elsevier Ltd. All rights reserved.

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《Bioorganic and medicinal chemistry》 |2016年第18期|4398-4405|共8页
作者
Radwan Mohamed O.; Sonoda Sachiko; Ejima TomohikoTanaka AyumiKoga RyokoOkamoto YoshinariFujita MikakoOtsuka Masami;
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作者单位

Kumamoto Univ, Dept Bioorgan Med Chem, Fac Life Sci, Chuo Ku, 5-1 Oe Honmachi, Kumamoto 8620973;

Kumamoto Univ, Res Inst Drug Discovery, Sch Pharm, Chuo Ku, 5-1 Oe Honmachi, Kumamoto 8620973, Japan;

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正文语种英语
中图分类药学;
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APOBEC3G; Host anti-viral factor; HIV; Zinc; Biotin-avidin technology; Molecular docking;

Zinc-mediated binding of a low-molecular-weight stabilizer of the host anti-viral factor apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G

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