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001-es BibID:BIBFORM094951
Első szerző:Mótyán János András (biokémikus, molekuláris biológus)
Cím:Specificity of the HIV-1 Protease on Substrates Representing the Cleavage Site in the Proximal Zinc-Finger of HIV-1 Nucleocapsid Protein / Mótyán János András, Miczi Márió, Stephen Oroszlan, Tőzsér József
ISSN:1999-4915 1999-4915
Megjegyzések:o explore the sequence context-dependent nature of the human immunodeficiency virus type 1 (HIV-1) protease's specificity and to provide a rationale for viral mutagenesis to study the potential role of the nucleocapsid (NC) processing in HIV-1 replication, synthetic oligopeptide substrates representing the wild-type and modified versions of the proximal cleavage site of HIV-1 NC were assayed as substrates of the HIV-1 protease (PR). The S1· substrate binding site of HIV-1 PR was studied by an in vitro assay using KIVKCF?NCGK decapeptides having amino acid substitutions of N17 residue of the cleavage site of the first zinc-finger domain, and in silico calculations were also performed to investigate amino acid preferences of S1· site. Second site substitutions have also been designed to produce "revertant" substrates and convert a non-hydrolysable sequence (having glycine in place of N17) to a substrate. The specificity constants obtained for peptides containing non-charged P1· substitutions correlated well with the residue volume, while the correlation with the calculated interaction energies showed the importance of hydrophobicity: interaction energies with polar residues were related to substantially lower specificity constants. Cleavable "revertants" showed one residue shift of cleavage position due to an alternative productive binding mode, and surprisingly, a double cleavage of a substrate was also observed. The results revealed the importance of alternative binding possibilities of substrates into the HIV-1 PR. The introduction of the "revertant" mutations into infectious virus clones may provide further insights into the potential role of NC processing in the early phase of the viral life-cycle.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
substrate specificity
nucleocapsid protein
viral proteins
viral proteases
human immunodeficiency virus
Megjelenés:Viruses-Basel. - 13 : 6 (2021), p. 1-14. -
További szerzők:Miczi Márió Oroszlan, Stephen Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész)
Pályázati támogatás:TKP2020-IKA-04
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