Reverse transcriptase

spinqualitylabelsall models HIV-1 reverse transcriptase P66 subunit (grey) and P51 subunit (green) complex with sulfate 3dlk Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Crystal Structure of unliganded HIV-1 Reverse transcriptase, 1hmv Introduction Reverse transcriptase (RT) or RNA-dependent DNA polymerase transcribes single-stranded RNA into double-stranded DNA. HIV-1 RT is from the human immunodeficiency virus and is a heterodimer of P66 and P51 subchains. The images at the left and at the right correspond to one representative RT structure, i.e. crystal structure of HIV-1 Reverse transcriptase (1hmv). P15 is its RNAse H domain. There are two types of inhibitors for RT: NNRTIs are the non-nucleoside inhibitors, and NRTIs are the nucleoide inhibitors. Being the protein that gives their name to Retroviruses, Reverse Transcriptase is, along with Protease and Integrase, the most important part of the protein system involved in the process of infection and reproduction for viruses like HIV, MuLV and AMV. RT 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. See also Transcription and RNA Processing HIV-1 Reverse Transcriptase in Complex with Nevirapine Phl p 2 AZT-resistant HIV-1 reverse transcriptase Catalytic Subunit of T. Castaneum TERT Polymerase. Telomerase Reverse Transcriptase Reverse Transcriptase is one of the CBI Molecules being studied in the University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground. -- CBI Molecular Playground Model -- Structure This hand-like heterodimer protein has an usual length of 1000 residues (560 in Chain A and 440 for B), a third of them involved in alpha helices and almost a quarter involved in beta sheets, showing α+β secondary structure domains. Chain A has an usual weight of 66KDa whereas Chain B is around 51KDa. These monomers are derived from the same gene, but p51 lacks the amino acids of one active site and has a different tertiary structure conformation compared to p66. Because of this, p51 is enzymatically inactive. There are five distinct structures within the p66 subchain that are used to describe the functions of RT: the fingers (residues 1–85 and 118–155), the palm (residues 86–117 and 156–236), the thumb (residues 237–318), the connection (319–426), and the RNase H (residues 427-end). The palm contains the main active site (residues 110, 185-186). Function As a RNA-dependent DNA Polymerase, Reverse Transcriptase 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 Polymerase active site that consist of two finger-like domains: one of them recognizes the initial nucleic acid by h-bond interactions with phosphate groups of the side chains, then both domains make a conformational change closing the recognition hole to allow the second domain with the support a Magnesium ion coordination system to begin the transcription process adding the specific DNA nucleotides. This change is allowed by a flexible zone between the two previous domains; it is used as a common pharmaceutical target site in order to prevent the change and therefore inhibit activity. This zone is the only zone of Chain A that has non-conserved aminoacids, giving the virus more drug resistance Link to Consurf Data Base for PDB Entry: 1JLB. As the same rate that the polymerization process occurs, the other active site known as the Ribonuclease H domain cleaves RNA, releasing the ssDNA that comes again through the Polymerase active site to become dsDNA (all this with a second Magnesium coordinative system, that allows non-specific recognition, just with phosphates). Finally, Chain B, despite the similar aminoacid sequence with Chain A, has no enzymatic activity; its function is possibly to stabilize and interact with both active sites by varying the length between them in order to synchronize both functions. This is the most general idea of the mechanism of action of Reverse Transcriptase; however the process remains unclear and new approaches are being reported . One of the principal issues about this protein compared to usual DNA polymerase (besides to the similarity with the Klenow fragment), is the lack of a correction mechanism (usually made by DNA PolIII in the DNA Polymerase); this deficiency increases the number of errors, producing more mutations and therefore giving more facultative and resistance ability to the virus.

3D Structures of Reverse transcriptase

Updated on 27-September-2017

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• HIV-1 reverse transcriptase P66/P51
  • 1hmv, DNA - P66/P51
    
  • 1hmv, Protease, Transcription and RNA Processing, HIV-1 Reverse Transcriptase in Complex with Nevirapine, Phl p 2, AZT-resistant HIV-1 reverse transcriptase, Catalytic Subunit of T. Castaneum TERT Polymerase, Telomerase Reverse Transcriptase, CBI Molecules, 4dg1, 4zhr - P66/P51 (mutant)
    
  • 3qip - P66/P51+NNRTI nevirapine + RNase H inhibitor
    
  • 3lp0, 3lp1, 3lp2, 1vrt, 3hvt - P66/P51+NNRTI nevirapine
    
  • 4i7f - P66/P51 + NNRTI nevirapine analog
    
  • 2hnd, 2hny, 1s1u, 1s1x, 1lw0, 1lwc, 1lwe, 1lwf, 1jlb, 1jlf, 1fkp - P66/P51 (mutant)+NNRTI nevirapine
    
  • 3m8p, 3mec - P66/P51+NNRTI etravirine
    
  • 3med - P66/P51 (mutant)+NNRTI etravirine
    
  • 3mee, 2zd1, 3qlh - P66/P51+NNRTI rilpivirine
    
  • 3meg, 2ze2, 3bgr, 4g1q, 4icl, 4id5, 4idk, 4ify, 4ig0, 4ig3, 4kfb - P66/P51 (mutant)+NNRTI rilpivirine
    
  • 1ikw, 1fk9 - P66/P51 +NNRTI efavirenz
    
  • 1jkh, 1ikv, 1fko - P66/P51 (mutant)+NNRTI efavirenz
    
  • 3dya, 3e01, 3drp - P66/P51+NNRTI pyrazole
    
  • 3drr, 3drs - P66/P51 (mutant)+NNRTI pyrazole
    
  • 3irx, 3is9, 3lak, 3lal, 3lam, 3lan, 3ffi, 3di6, 3dle, 3dlg, 2rki, 3c6t, 3c6u, 2rf2, 2vg5, 2vg6, 2vg7, 2opp, 1jlq, 1ep4, 1c0t, 1c0u, 1dtt, 1dtq, 1bqm, 1rt1, 1rt2, 1rev, 1rtj, 1vru, 1hnv, 1hni, 3t19, 5ki4, 5fdl, 5c24, 5c25, 4rw7, 5ter - P66/P51+NNRTI
    
  • 1s1t, 1s1v, 1s1w, 1s6p, 1s6q, 1s9e, 1s9g, 1suq, 1sv5, 3dm2, 3dmj, 3dok, 3dol, 2opq, 2opr, 2ops, 2ic3, 2hnz, 1jlg, 1bqn, 1uwb, 1tvr, 3qo9, 3t1a, 5c42, 5tw3, 4rw4, 4rw6, 4rw8 - P66/P51 (mutant)+NNRTI
    
  • 3kk1, 1c1b, 1rti, 4kv8 - P66/P51+ inhibitor
    
  • 2ynf, 2yng, 2ynf, 2yng, 4kko, 4lsl, 4lsn, 4mfb, 4o44, 4o4g - P66/P51 (mutant) + NNRTI
    
  • 1jla - P66/P51 (mutant)+ NRTI
    
  • 3ig1 - P66/P51+ inhibitor beta-thujaplicinol
    
  • 3i0r, 3i0s, 3m8q, 3isn, 3ith, 1c1c, 3nbp - P66/P51+ pyrimidine derivative
    
  • 1ikx, 4ko0, 4we1 - P66/P51 (mutant)+ pyrimidine derivative
    
  • 1tv6 - P66/P51+ pyridine derivative
    
  • 1jlc, 1iky, 1eet - P66/P51(mutant)+ pyridine derivative
    
  • 5cym, 5cyq - P66/P51 (mutant) + pyrazole derivative
    
  • 2b5j, 2ban, 2be2, 1rth - P66/P51+ pyridone derivative
    
  • 1lw2, 1rt3 - P66/P51 (mutant)+ NRTI
    
  • 1tkt, 1tkx, 1tkz, 1tl1, 1tl3 - P66/P51+ quinoline derivative
    
  • 5uv5 - P66/P51 (mutant) + quinoline derivative
    
  • 2b6a - P66/P51+ THR-50
    
  • 2i5j - P66/P51 (mutant)+hydrazone derivative
    
  • 1rt4, 1rt5, 1rt6, 1rt7 - P66/P51+ carboxanilide derivative
    
  • 1klm - P66/P51+piperazine derivative
    
• HIV-1 reverse transcriptase complex with DNA/RNA
  • 3kjv, 3kk3, 1r0a, 1n5y, 1n6q, 1hys, 5d3g, 5i3u - P66/P51+DNA
    
  • 1j5o, 1rtd, 3klf, 3v4i, 3v6d - P66/P51 (mutant)+DNA
    
  • 4r5p, 5j2n, 5txo, 5txp - P66/P51 (mutant) + nucleotide + DNA
    
  • 3v81 - P66/P51 (mutant)+DNA + NNRTI
    
  • 1hvu - P66/P51+RNA
    
  • 4b3o, 4b3p, 4b3q - P66/P51 + RNA + DNA
    
  • 4pqu - P66/P51 (mutant) + dATP + RNA + DNA
    
  • 4puo, 4pwd, 4q0b - P66/P51 (mutant) + nevirapine + RNA + DNA
    
  • 1t03, 1t05 - P66/P51+DNA+Fab+NRTI
    
  • 3jsm - P66/P51 (mutant)+DNA+NRTI
    
  • 2hmi - P66/P51 (mutant)+DNA+Fab
    
  • 2iaj - P66/P51 (mutant)+NRTI
    
  • 3kk2 - P66/P51+DNA+NRTI
    
  • 3jyt - P66/P51 (mutant)+DNA+NRTI
    
  • 4r5p, 5hlf, 5hp1, 5hro - P66/P51 + DNA + phosphonate inhibitor
    
• HIV-1 AZT-resistant reverse transcriptase P66/P51
  • 3kli - P66/P51 (mutant)
    
  • 3kle, 3klg, 3klh – P66/P51 (mutant) + DNA
• HIV-1 reverse transcriptase P66
  • 2jle – P66+NNRTI
    
  • 1har - P66 N-terminal
    
  • 5t82 - P66 thumb domain - NMR
    
• RT/ribonuclease H domain or Hiv-1 P15
  • 4mh8 – MmlvRT P80
    
  • 4m94, 4m95 – MmlvRT P80 catalytic fragment + DNA
    
  • 4ifv – Hiv1P66/P55 (mutant)
    
  • 2ykm, 2ykn – Hiv1P66 (mutant) + NNRTI
    
  • 4qag – Hiv1P66 + coumarin derivative
    
  • 4h4m – Hiv1P66/P55 (mutant) + NNRTI
    
  • 4h4o, 4rw4, 4rw6, 4rw7, 4rw8, 4rw9 – Hiv1P66/P51 (mutant) + NNRTI
    
  • 2ynh, 2yni, 4ncg – Hiv1P66/P51 + NNRTI
    
  • 1rdh, 1hrh, 5dzm – P15
    
  • 3lp3 – P15+inhibitor MK3
    
  • 3k2p – P15+inhibitor beta-thujaplicinol
    
  • 3hyf – P15+pyrimidine derivative
    
  • 1o1w – P15+Mg - NMR
    
• HIV-2 reverse transcriptase
  • 1mu2 - RT (mutant)
• Moloney murine leukemia virus reverse transcriptase
  • 1mml - MmlvRT residues 130-194
    
  • 2hb5 - MmlvRT residues 618-791
    
  • 1nnd - MmlvRT catalytic domain (mutant)
    
  • 2r2r, 2r2t, 2fjv, 2fjw, 2fjx, 1ztw, 2fvs, 2fvr, 2fvq, 2fvp, 1n4l, 4xo0, 4xpc, 4xpe – MmlvRT catalytic domain +DNA
    
  • 2r2s, 2r2u - MmlvRT catalytic domain +DNA+Co Bleomycin
    
  • 1ztt - MmlvRT catalytic domain +DNA+netropsin
    
  • 4mh8 – MmlvRT residues 683-1330 (mutant)
    
  • 1i6j, 1d0e, 1d1u, 1qaj, 1qai – MmlvRT N-terminal+DNA
    
  • 4xpc, 4xo0, 4xpe - MmlvRT catalytic domain + DNA
    
  • 3fsi - MmlvRT catalytic domain +DNA+trypanocidal
    
  • 5dmq, 5dmr - MmlvRT + ERF1
    
• XMRV reverse transcriptase
  • 3v1o, 3v1q – RNAse H domain
    
  • 3v1r – RNAse H domain + inhibitor
    
  • 4hkq – RT residues 658-1328 (mutant) + DNA + RNA
    
  • 2lsn – RT – Simian foamy virus - NMR
• Reverse transcriptase from telomerase

• • 2b2a - TtRT telomerase catalytic subunit (mutant) - Tetrahymena thermophila
    
  • 2r4g - TtRT telomerase catalytic subunit
    
  • 5c9h - TtRT catalytic subunit + DNA
    
  • 3du6, 3du5 - TcRT telomerase catalytic subunit - Tribolium castaneum
    
  • 3kyl - TcRT telomerase catalytic subunit + DNA
    
  • 4o26 – RT RNA-binding domain + RNA – rice fish
    
  • 4lmo - RT telomerase RNA-binding domain – tiger puffer
    
  • 5lgf - RT N-terminal - Ogataea polymorpha - NMR
    
  • 5ugw - hRT thumb domain
    
  • 5cqg - RT + inhibitor - red flour beetle
    

See Also

• Reverse Transcriptase at Wikipedia
• Molecule of the Month (09/2002) at RCSB Protein Data Bank
• List of Reverse Transcriptase articles at Proteopedia and at RCSB Protein Data Bank
• Model of Reverse Transcriptase as one of the CBI Molecules on the Molecular Playground
• See Transcription for additional Proteopedia articles on the subject.
• For additional information, see: Human Immunodeficiency Virus
• For additional information, see: Transcription and RNA Processing

Proteopedia Page Contributors and Editors (what is this?)

Daniel Moyano-Marino, Alexander Berchansky, Eric Martz, Amol Kapoor, Lynmarie K Thompson, David Canner, Brian Foley, Jaime Prilusky, Joel L. Sussman, Michal Harel