title: Addition of artificial salt bridge by Ile646Lys mutation in gp41 coiled-coil domain regulates 6-helical bundle formation.
abstract: HIV entry is mediated by the envelope glycoproteins gp120 and gp41. The gp41 subunit contains several functional domains: the N-terminal heptad repeat (NHR) domains fold a triple stranded coiled-coil forming a meta-stable prefusion intermediate. C-terminal heptad repeat (CHR) subsequently folds onto the hydrophobic grooves of the NHR coiled-coil to form a stable 6-helix bundle, which juxtaposes the viral and cellular membranes for fusion. The C34 which has 34 amino acid residues is known as the core structure in CHR. A highly anti-HIV peptide inhibitor derived from C34 was designed. An artificial salt bridge was added in the 6-helical bundle by substitution of lysine for Ile646. With a cholesterol modification at C-terminal, the inhibitor containing I646K mutation represented higher anti-viral activity than C34-cholesterol combination without mutation.
authors.affiliation: The Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Zhi-Wen
authors.initials: ZW
authors.lastname: Hu
authors.forename: Pei
authors.initials: P
authors.lastname: Tong
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Chen
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Zhao
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D012492:Salts / Q000737:chemistry*; D055672:Static Electricity; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010455:Peptides; D012492:Salts