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001-es BibID:BIBFORM040794
Első szerző:Tőzsér József (molekuláris biológus, biokémikus, vegyész)
Cím:Specifity of retroviral proteinases based on substrates containing tyrosine and proline at the site of cleavage / Tőzsér József
Dátum:1997
ISSN:1532-2807
Megjegyzések:The retroviral proteinase (PR) plays crucial roles in the viral life cycle, therefore it is a target for chemotherapy. However, resistance rapidly develops due to frequent mutations. Studies to determine the common features of the specificity of different retroviral PRs may help to design broad spectrum inhibitors and reduce the possibility of viable mutants. We have studied the specificity of various retroviral proteinases including those the PR of HIV-1, HIV-2, equine infectious anemia virus and avian myeloblastosis virus using oligopeptide substrates. A series of oligopeptides containing substitutions in a sequence Val-Ser-Gln-Asn-Tyr*Pro-Ile-Val-Gln (asterisk indicates the site of cleavage) representing a naturally occurring cleavage site in HIV-1 was used to characterize the seven substrate binding subsites of the enzymes. The unsubstituted substrate is a typical class 1 cleavage site substrate containing an aromatic amino acid and a proline residue at the site of cleavage. The largest differences in kinetics of substrate hydrolysis were obtained with peptides containing substitutions of the Ser and Asn residues. Detailed analysis of the results by molecular modeling and comparison with previously reported data revealed the common characteristics of the specificity of the PRs as well as its strong dependence on the sequence context of the substrate. However, molecular modeling in many cases provided explanation for the sequence context dependence. Also, comparison of the specificity of the enzymes suggests that the specificity of HIV-1 and -2 PRs is rather exceptional preferring hydrophilic residues at the most discriminative positions while other PRs prefer hydrophobic residues.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Pathology & Oncology Research. - 3 : 2 (1997), p. 142-146. -
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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