title: Zinc-binding site of human immunodeficiency virus 2 Vpx prevents instability and dysfunction of the protein.
abstract: Human immunodeficiency virus 2 Vpx coordinates zinc through residues H39, H82, C87 and C89. We reported previously that H39, H82 and C87 mutants maintain Vpx activity to facilitate the degradation of SAMHD1. Herein, the expression of Vpx mutants in cells was examined in detail. We demonstrated that the zinc-binding site stabilizes the protein to keep its function in virus growth when low levels of Vpx are expressed. At higher levels of expression, Vpx aggregation could occur, and zinc binding would suppress such aggregation. Among the amino acids involved in zinc coordination, H39 plays the most critical role. In summary, zinc binding appears to mitigate flexibility of the three-helix fold of Vpx, thereby preventing dysfunction.
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Koga
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Fujino
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Shimagaki
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Halil Ibrahim
authors.initials: HI
authors.lastname: Ciftci
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kamo
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tateishi
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Otsuka
authors.affiliation: Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Mikako
authors.initials: M
authors.lastname: Fujita
mesh_terms: D001665:Binding Sites / Q000235:genetics; D057809:HEK293 Cells; D015498:HIV-2 / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D017510:Protein Folding; D055550:Protein Stability; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry* / Q000235:genetics; D015032:Zinc / Q000737:chemistry*
chemical_list: C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D015032:Zinc