title: Allosteric regulation of HIV-1 reverse transcriptase by ATP for nucleotide selection.
abstract: BACKGROUND
  Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is a DNA polymerase that converts viral RNA genomes into proviral DNAs. How HIV-1 RT regulates nucleotide selectivity is a central issue for genetics and the nucleoside analog RT inhibitor (NRTI) resistance of HIV-1.
  
  
  RESULTS
  Here we show that an ATP molecule at physiological concentrations acts as an allosteric regulator of HIV-1 RT to decrease the K(m) value of the substrate, decrease the k(cat) value, and increase the K(i) value of NRTIs for RT. Computer-assisted structural analyses and mutagenesis studies suggested the positions of the ATP molecule and NRTI-resistance mutations during a catalytic reaction, which immediately predict possible influences on nucleotide insertion into the catalytic site, the DNA polymerization, and the excision reaction.
  
  
  CONCLUSIONS
  These data imply that the ATP molecule and NRTI mutations can modulate nucleotide selectivity by altering the fidelity of the geometric selection of nucleotides and the probability of an excision reaction.
authors.affiliation: Pathogen Genomics Center, National Institute of Infectious Diseases, Musashi Murayama-shi, Tokyo, Japan. yokoyama@nih.go.jp
authors.forename: Masaru
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mori
authors.forename: Hironori
authors.initials: H
authors.lastname: Sato
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000494:Allosteric Regulation; D055162:Biocatalysis; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology
chemical_list: D018894:Reverse Transcriptase Inhibitors; D000255:Adenosine Triphosphate; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase