title: A single deletion at position 134, 135, or 136 in the beta 7-beta 8 loop of the p51 subunit of HIV-1 RT disrupts the formation of heterodimeric enzyme.
abstract: The human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is a heterodimeric enzyme composed of p66 and p51 subunits. Earlier, we showed that the beta7-beta8 loop of p51 is crucial for polymerase activity of HIV-1 RT as either deletion or Ala substitution of amino acids in the beta7-beta8 loop spanning residues 136-139 in the p51 subunit impaired dimerization and, in turn, polymerase function of the enzyme (Pandey et al. 2001 Biochemistry 40: 9505-9512). In the present study, we generated subunit-specific single-deletion mutants at positions 134, 135, 136, or 137 and examined their effects on the heterodimerization, binary complex formation, and polymerase functions of the enzyme. We found that among these four residues, Ser134, Ile135, and Asn136 in the beta7-beta8 loop of the p51 subunit are crucial residues for dimerization and polymerase function of the enzyme, but have no impact when specifically deleted from the p66 subunit. These results demonstrate the beta7-beta8 loop of the p51 subunit in the formation of stable, functional heterodimeric enzyme which could be an attractive target for anti-HIV-1 drug development.
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for the Study of Emerging and Re-Emerging Pathogens, UMDNJ-New Jersey Medical School, 185-South Orange Avenue, Newark, New Jersey 07103, USA.
authors.forename: Alok
authors.initials: A
authors.lastname: Upadhyay
authors.forename: Nootan
authors.initials: N
authors.lastname: Pandey
authors.forename: Chaturbhuj A
authors.initials: CA
authors.lastname: Mishra
authors.forename: Tanaji T
authors.initials: TT
authors.lastname: Talele
authors.forename: Virendra N
authors.initials: VN
authors.lastname: Pandey
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D019281:Dimerization; D054303:HIV Reverse Transcriptase / Q000737:chemistry* / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
chemical_list: D021122:Protein Subunits; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase