Reverse transcriptase
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Being the protein that gives their name to Retroviruses, Reverse Transcriptase is, in company of Protease and Integrase, the most important part of the protein system involved in the process of infection of viruses like HIV [1], MuLV and AMV, and has the unusual property of transcribing ssRNA into dsDNA going against the Central Dogma of Molecular Biology. Since its discovery in 1970, the study of its properties and mechanisms of action have been of high interest among the scientific community due to the unique properties that makes it an important medical target enzyme and important tool for genetic engineering applications like RT-PCR in the construction of cDNA libraries.
StructureStructure
This hand-like protein that has an usual length of 1000 residues(560 in Chain A and 440 for B), the third of them involved in alpha helical and almost a quarter in beta sheets, showing α+β domains; chain A with an usual weight of 65KDa contains the two actives sites and has the most conserved aminoacids, whereas chain B is around 50KDa and has more variable areas, result of drug resistant and function related evolution. [2]
FunctionFunction
As a RNA-dependent DNA Polymerase, is able to recognize the initial RNA, transcribe it to ssDNA, cleave the remaining RNA and then build up the dsDNA, to do this the protein has two active catalytic zones. Chain A has the that consist of two finger-like domains, one of them recognizes the initial nucleic acid possibly by h-bonds interactions with phosphate groups of the side chains, then both domains make a conformational change closing the recognition hole to allow the second domain begin the transcription process. As the same rate that this process occur, the other active site known as the Ribonuclease H domain, cleaves the RNA releasing the ssDNA that comes again trough the Polymerase active site to become dsDNA.
See AlsoSee Also
- Molecule of the Month (09/2002) at RCSB PDB
- List of Reverse Transcriptase articles at Proteopedia and at RCSB PDB
- Reverse Transcriptase at Wikipedia