This article was accepted into the corpus but its outbound wikilinks were never NER-processed — typical at the deepest BFS hop or when the run's entity cap was reached. No expansion funnel to show.
| HIV-1 reverse transcriptase | |
|---|---|
| Name | HIV-1 reverse transcriptase |
| EC number | 2.7.7.49 |
| Organism | Human immunodeficiency virus type 1 |
| Subunits | p66 and p51 heterodimer |
| Cofactors | Mg2+, Mn2+ |
| Synonyms | RT, HIV-1 RT |
HIV-1 reverse transcriptase is a heterodimeric enzyme essential for replication of Human immunodeficiency virus and a primary target for antiretroviral therapy, studied across laboratories such as Cold Spring Harbor Laboratory, National Institutes of Health, and Institut Pasteur. Early biochemical characterization involved teams at Rockefeller University, University of Oxford, and Harvard University, while structural elucidation relied on crystallography groups at Stanford University and Max Planck Society. The enzyme links discoveries and clinical practice spanning institutions like Centers for Disease Control and Prevention, World Health Organization, and pharmaceutical companies including GlaxoSmithKline, Gilead Sciences, and Pfizer.
HIV-1 reverse transcriptase comprises an asymmetric heterodimer of p66 and p51 subunits resolved by X-ray crystallography from labs including Imperial College London, Massachusetts Institute of Technology, and Scripps Research Institute. The p66 subunit contains polymerase and RNase H domains analogous to polymerases studied at Cold Spring Harbor Laboratory, whereas p51 provides structural support similar to scaffolding roles observed in complexes at European Molecular Biology Laboratory and Max Planck Institute. The polymerase domain is subdivided into fingers, palm, and thumb subdomains as in polymerases characterized at Johns Hopkins University, University of Cambridge, and University of California, San Francisco, with conserved motifs identified by comparative work from Yale University and University of Tokyo. The RNase H domain, structurally compared to RNase H enzymes from ETH Zurich and University of Basel, contains catalytic residues coordinating divalent cations reported by researchers at University of Pennsylvania and Columbia University.
Polymerization proceeds through a two-metal-ion mechanism described in foundational studies at Princeton University, Caltech, and University of Chicago, with Mg2+ or Mn2+ cofactors coordinated by residues identified by investigators at Duke University and University of Michigan. Nucleotide incorporation involves conformational changes in fingers and thumb regions, paralleling mechanistic models from Tokyo Institute of Technology, University of Sydney, and Monash University. RNase H catalysis cleaves RNA in RNA/DNA hybrids using metal-assisted hydrolysis, a process elaborated by groups at Karolinska Institute, Uppsala University, and University of Toronto. Kinetic parameters and pre-steady-state analyses were refined in studies at University of California, Berkeley, University of Washington, and University of Illinois.
HIV-1 reverse transcriptase converts single-stranded viral RNA into double-stranded proviral DNA, enabling integration by HIV-1 integrase into host genomes targeted in cell lines used at National Cancer Institute, Memorial Sloan Kettering Cancer Center, and Fred Hutchinson Cancer Center. Its activity interfaces with viral proteins such as Gag, Pol, and host factors exemplified by studies at University College London, McGill University, and Karolinska Institutet. Reverse transcription occurs in reverse transcription complexes tracked in microscopy work at Max Delbrück Center for Molecular Medicine, Weizmann Institute, and ETH Zurich, influencing latency studies pursued at University of California, San Diego, Vanderbilt University, and University of Pennsylvania.
Reverse transcriptase is a principal target for antiretroviral drugs developed by teams at Roche, Merck & Co., and Bristol Myers Squibb, with clinical management guided by organizations like World Health Organization, United States Food and Drug Administration, and European Medicines Agency. Resistance arises through mutations mapped by surveillance programs at Centers for Disease Control and Prevention, Joint United Nations Programme on HIV/AIDS, and research consortia including Stanford HIV Drug Resistance Database contributors from University of Cambridge and University of Liverpool. Structural bases of resistance were elucidated by crystallographers at Scripps Research Institute, Massachusetts General Hospital, and Institut Pasteur, informing treatment guidelines from National Institutes of Health and British HIV Association.
Nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine, lamivudine, and tenofovir were developed with input from laboratories at Columbia University, University of North Carolina at Chapel Hill, and Gilead Sciences; non-nucleoside inhibitors (NNRTIs) including nevirapine, efavirenz, and rilpivirine emerged from programs at Janssen Pharmaceuticals, Boehringer Ingelheim, and Merck Research Laboratories. Biochemical inhibition profiles were characterized in assays at National Institutes of Health, Emory University, and University of California, San Francisco, while clinical trials occurred at centers such as Mayo Clinic, Cleveland Clinic, and Guy's and St Thomas' NHS Foundation Trust. Drug-drug interactions and pharmacokinetics were addressed in studies at University of Liverpool, University of Barcelona, and Karolinska Institute.
Sequence diversity of reverse transcriptase among clades A, B, C, and others was cataloged by global initiatives including Los Alamos National Laboratory and contributors at University of Sao Paulo, Stellenbosch University, and University of Nairobi. Key resistance-associated mutations such as M184V, K65R, and K103N were identified in cohorts studied at Harvard Medical School, Johns Hopkins University, and University of Cape Town, with implications for therapy in guidelines from World Health Organization and United States Department of Health and Human Services. Phylogenetic and population-level analyses employed methods developed at University of Edinburgh, Imperial College London, and Durham University.
Biochemical assays including polymerase and RNase H activity assays have been standardized in laboratories at National Institutes of Health, European Molecular Biology Laboratory, and Wellcome Sanger Institute; single-molecule techniques were advanced at Max Planck Institute for Biophysical Chemistry, University of Geneva, and Harvard University. High-resolution structures by X-ray crystallography and cryo-electron microscopy were produced by teams at Stanford University, Scripps Research Institute, and EMBL-EBI, complemented by computational modeling from Broad Institute, Los Alamos National Laboratory, and University of California, San Diego. Assay platforms for resistance testing are implemented in clinical labs at Mayo Clinic, Johns Hopkins Hospital, and University College London Hospitals.
Category:Viral enzymes