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Journal of Virology, October 2008, p. 10111-10117, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.00418-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Amino Acid Preferences of Retroviral Proteases for Amino-Terminal Positions in a Type 1 Cleavage Site{triangledown} ,{ddagger}

Helga Eizert,1,{dagger} Pálma Bander,1,{dagger} Péter Bagossi,1 Tamás Sperka,1 Gabriella Miklóssy,1 Péter Boross,1 Irene T. Weber,2 and József Tözsér1*

Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Egyetem tér 1, Life Science Building, Hungary,1 Department of Biology, Molecular Basis of Disease Program, Georgia State University, Atlanta, Georgia2

Received 26 February 2008/ Accepted 26 July 2008

The specificities of the proteases of 11 retroviruses were studied using a series of oligopeptides with amino acid substitutions in the P1, P3, and P4 positions of a naturally occurring type 1 cleavage site (Val-Ser-Gln-Asn-Tyr{downarrow}Pro-Ile-Val-Gln) in human immunodeficiency virus type 1 (HIV-1). Previously, the substrate specificity of the P2 site was studied for the same representative set of retroviral proteases, which included at least one member from each of the seven genera of the family Retroviridae (P. Bagossi, T. Sperka, A. Fehér, J. Kádas, G. Zahuczky, G. Miklóssy, P. Boross, and J. Tözsér, J. Virol. 79:4213-4218, 2005). Our enzyme set comprised the proteases of HIV-1, HIV-2, equine infectious anemia virus, avian myeloblastosis virus (AMV), Mason-Pfizer monkey virus, mouse mammary tumor virus (MMTV), Moloney murine leukemia virus, human T-lymphotropic virus type 1, bovine leukemia virus, walleye dermal sarcoma virus, and human foamy virus. Molecular models were used to interpret the similarities and differences in specificity between these retroviral proteases. The results showed that the retroviral proteases had similar preferences (Phe and Tyr) for the P1 position in this sequence context, but differences were found for the P3 and P4 positions. Importantly, the sizes of the P3 and P4 residues appear to be a major contributor for specificity. The substrate specificities correlated well with the phylogenetic tree of the retroviruses. Furthermore, while the specificities of some enzymes belonging to different genera appeared to be very similar (e.g., those of AMV and MMTV), the specificities of the primate lentiviral proteases substantially differed from that observed for a nonprimate lentiviral protease.

* Corresponding author. Mailing address: University of Debrecen, Department of Biochemistry and Molecular Biology, Nagyerdei krt. 98, Debrecen H-4012, Hungary. Phone: 36-52-416432. Fax: 36-52-314989. E-mail: tozser{at}dote.hu

{triangledown} Published ahead of print on 13 August 2008.

{ddagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{dagger} These authors contributed equally to this work.

Journal of Virology, October 2008, p. 10111-10117, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.00418-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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