Amino acid preferences for a critical substrate binding subsite of retroviral proteases in type 1 cleavage sites

P. Bagossi, Tamás Sperka, Anita Fehér, János Kádas, Gábor Zahuczky, Gabriella Miklóssy, Péter Boross, J. Tőzsér

Research output: Contribution to journalArticle

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Abstract

The specificities of the proteases of 11 retroviruses representing each of the seven genera of the family Retroviridae were studied using a series of oligopeptides with amino acid substitutions in the P2 position of a naturally occurring type 1 cleavage site (Val-Ser-Gln-Asn-Tyr ↓ Pro-Ile-Val-Gln; the arrow indicates the site of cleavage) in human immunodeficiency virus type 1 (HIV-1). This position was previously found to be one of the most critical in determining the substrate specificity differences of retroviral proteases. Specificities at this position were compared for HIV-1, HIV-2, equine infectious anemia virus, avian myeloblastosis virus, Mason-Pfizer monkey virus, mouse mammary tumor virus, Moloney murine leukemia virus, human T-cell leukemia virus type 1, bovine leukemia virus, human foamy virus, and walleye dermal sarcoma virus proteases. Three types of P2 preferences were observed: a subgroup of proteases preferred small hydrophobic side chains (Ala and Cys), and another subgroup preferred large hydrophobic residues (Ile and Leu), while the protease of HIV-1 preferred an Asn residue. The specificity distinctions among the proteases correlated well with the phylogenetic tree of retroviruses prepared solely based on the protease sequences. Molecular models for all of the proteases studied were built, and they were used to interpret the results. While size complementarities appear to be the main specificity-determining features of the S2 subsite of retroviral proteases, electrostatic contributions may play a role only in the case of HIV proteases. In most cases the P2 residues of naturally occurring type 1 cleavage site sequences of the studied proteases agreed well with the observed P2 preferences.

Original languageEnglish
Pages (from-to)4213-4218
Number of pages6
JournalJournal of Virology
Volume79
Issue number7
DOIs
Publication statusPublished - Apr 2005

Fingerprint

Peptide Hydrolases
proteinases
Amino Acids
amino acids
Retroviridae
Human immunodeficiency virus 1
HIV-1
Epsilonretrovirus
Walleye dermal sarcoma virus
Simian foamy virus
Mason-Pfizer monkey virus
Avian myeloblastosis virus
Equine infectious anemia virus
Avian Myeloblastosis Virus
Deltaretrovirus
Mouse mammary tumor virus
Bovine Leukemia Virus
HIV Protease
Moloney murine leukemia virus
Human immunodeficiency virus 2

ASJC Scopus subject areas

  • Immunology

Cite this

Amino acid preferences for a critical substrate binding subsite of retroviral proteases in type 1 cleavage sites. / Bagossi, P.; Sperka, Tamás; Fehér, Anita; Kádas, János; Zahuczky, Gábor; Miklóssy, Gabriella; Boross, Péter; Tőzsér, J.

In: Journal of Virology, Vol. 79, No. 7, 04.2005, p. 4213-4218.

Research output: Contribution to journalArticle

Bagossi, P. ; Sperka, Tamás ; Fehér, Anita ; Kádas, János ; Zahuczky, Gábor ; Miklóssy, Gabriella ; Boross, Péter ; Tőzsér, J. / Amino acid preferences for a critical substrate binding subsite of retroviral proteases in type 1 cleavage sites. In: Journal of Virology. 2005 ; Vol. 79, No. 7. pp. 4213-4218.
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