p15gag Proteinase of Myeloblastosis Associated Virus: Specificity Studies with Substrate Based Inhibitors
The key role of retrovirus-encoded proteinases in limited proteolysis of polyprotein precursors, a prerequisite of the formation of mature infectious virions, makes these enzymes attractive targets of specific inhibitors. A rational basis for the design of such inhibitors requires detailed knowledge of the proteinase-inhibitor interactions at the level of three-dimensional structures. Such data are available so far only for the HIV-1 proteinase whose crystal complexes with some inhibitors were subject of X-ray studies.1 The absence of such information on the myeloblastosis associated virus (MAV) proteinase, another retroviral aspartate proteinase, together with the need of finding a tight-binding yet hydrophilic inhibitor for both X-ray studies and titration of its active site, led us to investigate the interactions of the proteinase with various classes of custom-synthesized inhibitors.
KeywordsGeneral Aspartic Proteinase Myeloblastosis Associate Virus Bulky Hydrophobic Side Chain Chymosin Inhibitor Small Hydrophobic Side Chain
Unable to display preview. Download preview PDF.
- 3.P. Štrop, I. Pichova, V. Kostka, F. Kapralek and J. Sedláček, Isolation and characterization of pl5gag proteinase of myeloblastosis associated virus expressed in E. coli, in: “Proteinases of Retroviruses”, V. Kostka, ed., W. de Gruyter, Berlin, New York (1989).Google Scholar
- 4.D. H. Coy, Y. Sasaki, W. A. Murphy and M. Heiman, Facile solid-phase preparation of peptides containing the CH2NH peptide bond isostere and application to the synthesis of somatostatin (SRIF) octapeptide analogues, in: “Peptides 1986”, D. Theodoropoulos, ed., W. de Gruyter, Berlin, New York (1987).Google Scholar
- 6.S. I. Foundling, F. R. Salemme, B. Korant, J. J. Wendolski, P. C. Weber, A. C. Trehame, M. C. Schadt, M. Jaskólski, M. Miller, A. Wlodawer, P. Štrop, V. Kostka, J. Sedláček and D. H. Ohlendorf, Crystal structure of a retroviral proteinase from avian Myeloblastosis Associated Virus, in: “Viral Proteinases as Targets for Chemotherapy”, H. G. Kräusslich, S. Oroszlan, and E. Wimmer, eds., Cold Spring Harbor Laboratory, Cold Spring Harbor (1989).Google Scholar
- 7.P. Štrop, M. Horejsi, J. Konvalinka, R. Škrabana, J. Velek, I. Blaha, V. Černá, I. Pichova, L. Pavlíčková, M. Andreansky, M. Fabry, V. Kostka and J. Sedláček, Protein-engineered proteinase of myeloblastosis associated virus: an enzyme of high activity and HIV-1 proteinase-like specificity, preceeding chapter.Google Scholar