A Comparative Analysis of the Binding Affinity of HIV-1 Reverse Transcriptase to DNA vs. RNA Substrates

dc.contributor.advisorDeStefano, Jeffrey Jen_US
dc.contributor.authorOlimpo, Jeffrey T.en_US
dc.contributor.departmentCell Biology & Molecular Geneticsen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2010-10-07T06:13:26Z
dc.date.available2010-10-07T06:13:26Z
dc.date.issued2010en_US
dc.description.abstractHuman immunodeficiency virus reverse transcriptase (HIV-RT) binds more stably in binary complexes with RNA-DNA versus DNA-DNA. Current results indicate that only the -2 and -4 RNA nucleotides (-1 hybridized to the 3´ recessed DNA base) are required for stable binding to RNA-DNA, and even a single RNA nucleotide conferred significantly greater stability than DNA-DNA. Replacing 2´- hydroxyls on pivotal RNA bases with 2´-O-methyls did not affect stability, indicating that interactions between hydroxyls and RT amino acids do not stabilize binding. Avian myeloblastosis and Moloney murine leukemia virus RTs also bound more stably to RNA-DNA, but the difference was less pronounced than with HIV-RT. We propose that the H- versus B-form structures of RNA-DNA and DNA-DNA, respectively, allow the former to conform more easily to HIV-RT's binding cleft, leading to more stable binding. Biologically, this may aid in degradation of RNA fragments that remain after DNA synthesis.en_US
dc.identifier.urihttp://hdl.handle.net/1903/10958
dc.subject.pqcontrolledBiology, Virologyen_US
dc.subject.pqcontrolledChemistry, Biochemistryen_US
dc.subject.pquncontrolledAIDSen_US
dc.subject.pquncontrolledDNAen_US
dc.subject.pquncontrolledHuman Immunodeficiency Virusen_US
dc.subject.pquncontrolledRetrovirusen_US
dc.subject.pquncontrolledReverse Transcriptaseen_US
dc.subject.pquncontrolledRNAen_US
dc.titleA Comparative Analysis of the Binding Affinity of HIV-1 Reverse Transcriptase to DNA vs. RNA Substratesen_US
dc.typeThesisen_US

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