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Biochemistry. 1991 May 14;30(19):4663-71.

Structural and evolutionary relationships between retroviral and eucaryotic aspartic proteinases.

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Macromolecular Structure Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702.


Three-dimensional crystal structures of the homologous retroviral proteinases from Rous sarcoma virus (RSV PR) and from human immunodeficiency virus (HIV-1 PR) are to a large extent similar and bear close resemblance to the six known structures of the bilobal fungal and mammalian aspartic proteinases. Systematic three-dimensional structural superpositions were carried out between the retroviral and the eucaryotic aspartic proteinases. Both retroviral enzymes were found to be similarly related to their fungal and mammalian counterparts. The most strongly conserved parts correspond to those regions in the N- and C-domains of the eucaryotic enzymes that are related by the interdomain dyad and consist of a combination of secondary structural elements that form the psi loop-alpha helix motif at the active sites of the aspartic proteinases. The retroviral proteinase monomer exhibits nearly the same degree of structural equivalence to the N- and C-domains of the eucaryotic enzymes. In light of the deduced structural relationships between HIV-1 PR and RSV PR, sequence alignments were performed for a number of retroviral proteinases from different subfamilies. There are three highly conserved amino acid sequence stretches, of which two belong to the psi loop-alpha helix motif, that bear moderate sequence similarity with the eucaryotic enzymes. The third conserved sequence stretch among the retroviral proteinases belongs to the flap and bears no resemblance to the flap sequences in the eucaryotic enzymes. The interdomain antiparallel beta sheet in the cellular enzymes differs from the intersubunit beta sheet in the number, arrangement, and directionality of strands, suggesting the possibility of convergent evolution.(ABSTRACT TRUNCATED AT 250 WORDS).

[Indexed for MEDLINE]

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