Open AccessEffect of substrate residues on the P2′ preference of retroviral proteinases
Author(s) -
Boross Péter,
Bagossi Péter,
Copeland Terry D.,
Oroszlan Stephen,
Louis John M.,
Tözsér József
Publication year - 1999
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1999.00687.x
Subject(s) - equine infectious anemia , cleavage (geology) , capsid , retrovirus , murine leukemia virus , peptide sequence , sequence (biology) , chemistry , virus , biology , stereochemistry , biochemistry , virology , gene , paleontology , fracture (geology)
The substrate sequence requirements for preference toward P2′ Glu residue by human immunodeficiency virus type 1 (HIV‐1) proteinase were studied in both the matrix protein/ capsid protein (MA/CA) and CA/p2 cleavage site sequence contexts. These sequences represent typical type 1 (–aromatic*Pro–) and type 2 (–hydrophobic* hydrophobic–) cleavage site sequences, respectively. While in the type 1 sequence context, the preference for P2′ Glu over Ile or Gln was found to be strongly dependent on the ionic strength and the residues being outside the P2–P2′ region of the substrate, it remained preferable in the type 2 substrates when typical type 1 substrate sequence residues were substituted into the outside regions. The pH profile of the specificity constants suggested a lower pH optimum for substrates having P2′ Glu in contrast to those having uncharged residues, in both sequence contexts. The very low frequency of P2′ Glu in naturally occurring retroviral cleavage sites of various retroviruses including equine infectious anemia virus (EIAV) and murine leukemia virus (MuLV) suggests that such a residue may not have a general regulatory role in the retroviral life cycle. In fact, unlike HIV‐1 and HIV‐2, EIAV and MuLV proteinases do not favor P2′ Glu in either the MA/CA or CA/p2 sequence contexts.