Reverse transcriptase: Difference between revisions

From Proteopedia
Jump to navigationJump to search
Michal Harel (talk | contribs)
No edit summary
Michal Harel (talk | contribs)
No edit summary
Line 1: Line 1:
<StructureSection load='3dlk' size='340' side='right' caption='HIV-1 reverse transcriptase P66 subunit (grey) and P51 subunit (green) complex with sulfate [[3dlk]]' scene=''>
<StructureSection load='3dlk' size='340' side='right' caption='HIV-1 reverse transcriptase P66 subunit (grey) and P51 subunit (green) complex with sulfate [[3dlk]]' scene=''>


[[Image:1hmv1.png|left|200px|thumb|Crystal Structure of unliganded HIV-1 Reverse transcriptase, [[1hmv]]]]
==Introduction==
==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 [[Hiv protease|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.
[[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 [[Hiv protease|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.
Line 42: Line 41:


**[[3dlk]], [[1hmv]] - P66/P51<br />
**[[3dlk]], [[1hmv]] - P66/P51<br />
**[[1mu2]], [[1jle]], [[1hpz]], [[1hqu]], [[1qe1]], [[1dlo]], [[2wom]], [[2won]], [[3tam]], [[4dg1]], [[4zhr]] - P66/P51 (mutant)<br />
**[[1mu2]], [[1jle]], [[1hpz]], [[1hqu]], [[1qe1]], [[1dlo]], [[2wom]], [[2won]], [[3tam]], [[4dg1]], [[4zhr]], [[4ifv]] - P66/P51 (mutant)<br />
**[[3qip]] - P66/P51+NNRTI nevirapine + RNase H inhibitor<br />  
**[[3qip]] - P66/P51+NNRTI nevirapine + RNase H inhibitor<br />  
**[[3lp0]], [[3lp1]], [[3lp2]], [[1vrt]], [[3hvt]] - P66/P51+NNRTI nevirapine<br />  
**[[3lp0]], [[3lp1]], [[3lp2]], [[1vrt]], [[3hvt]] - P66/P51+NNRTI nevirapine<br />  
Line 55: Line 54:
**[[3dya]], [[3e01]], [[3drp]] - P66/P51+NNRTI pyrazole<br />
**[[3dya]], [[3e01]], [[3drp]] - P66/P51+NNRTI pyrazole<br />
**[[3drr]], [[3drs]] - P66/P51 (mutant)+NNRTI pyrazole<br />
**[[3drr]], [[3drs]] - P66/P51 (mutant)+NNRTI pyrazole<br />
**[[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<br />
**[[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]], [[5k14]], [[2ynh]], [[2yni]], [[4ncg]] - P66/P51+NNRTI<br />
**[[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<br />
**[[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]], [[2ynf]], [[2yng]], [[2ynf]], [[2yng]], [[4kko]], [[4lsl]], [[4lsn]], [[4mfb]], [[4o44]], [[4o4g]], [[1lw2]], [[1rt3]], [[6duh]], [[6dug]], [[6duf]], [[6cgf]], [[6c0r]], [[1jla]], [[6c0p]], [[6c0o]], [[6c0n]], [[6c0l]], [[6c0k]], [[6c0j]], [[5vqz]], [[5vqy]], [[5vqx]], [[5vqw]], [[5vqv]], [[5vqu]], [[5vqt]], [[5vqs]], [[5vqr]], [[5vqq]], [[5tep]], [[2ykm]], [[2ykn]], [[4h4m]], [[4h4o]], [[4rw4]], [[4rw6]], [[4rw7]], [[4rw8]], [[4rw9]]  - P66/P51 (mutant)+NNRTI<br />
**[[4qag]] – Hiv1P66 + coumarin derivative <br />
**[[3kk1]], [[1c1b]], [[1rti]], [[4kv8]] - P66/P51+ inhibitor<br />
**[[3kk1]], [[1c1b]], [[1rti]], [[4kv8]] - P66/P51+ inhibitor<br />
**[[2ynf]], [[2yng]], [[2ynf]], [[2yng]], [[4kko]], [[4lsl]], [[4lsn]], [[4mfb]], [[4o44]], [[4o4g]] - P66/P51 (mutant) + NNRTI <br />
**[[2ynf]], [[2yng]], [[2ynf]], [[2yng]], [[4kko]], [[4lsl]], [[4lsn]], [[4mfb]], [[4o44]], [[4o4g]] - P66/P51 (mutant) + NNRTI <br />
**[[1jla]] - P66/P51 (mutant)+ NRTI<br />
**[[1jla]] - P66/P51 (mutant)+ NRTI<br />
**[[3ig1]] - P66/P51+ inhibitor beta-thujaplicinol<br />
**[[3ig1]] - P66/P51+ inhibitor beta-thujaplicinol<br />
**[[3i0r]], [[3i0s]], [[3m8q]], [[3isn]], [[3ith]], [[1c1c]], [[3nbp]]  - P66/P51+ pyrimidine derivative<br />
**[[3i0r]], [[3i0s]], [[3m8q]], [[3isn]], [[3ith]], [[1c1c]], [[3nbp]], [[5vz6]]  - P66/P51+ pyrimidine derivative<br />
**[[1ikx]], [[4ko0]], [[4we1]] - P66/P51 (mutant)+ pyrimidine derivative<br />
**[[1ikx]], [[4ko0]], [[4we1]], [[6aoc]], [[5tuq]] - P66/P51 (mutant)+ pyrimidine derivative<br />
**[[1tv6]] - P66/P51+ pyridine derivative<br />
**[[1tv6]] - P66/P51+ pyridine derivative<br />
**[[6eli]] - P66/P51+ pyridine derivative + rilpivirine + gag-pol polyprotein<br />
**[[1jlc]], [[1iky]], [[1eet]] - P66/P51(mutant)+ pyridine derivative<br />
**[[1jlc]], [[1iky]], [[1eet]] - P66/P51(mutant)+ pyridine derivative<br />
**[[5cym]], [[5cyq]] - P66/P51 (mutant) + pyrazole derivative<br />
**[[5cym]], [[5cyq]] - P66/P51 (mutant) + pyrazole derivative<br />
**[[2b5j]], [[2ban]], [[2be2]], [[1rth]] - P66/P51+ pyridone derivative<br />
**[[2b5j]], [[2ban]], [[2be2]], [[1rth]] - P66/P51+ pyridone derivative<br />
**[[5j1e]], [[5hbm]] - P66/P51 (mutant) + pyridone derivative<br />
**[[1lw2]], [[1rt3]] - P66/P51 (mutant)+ NRTI<br />
**[[1lw2]], [[1rt3]] - P66/P51 (mutant)+ NRTI<br />
**[[1tkt]], [[1tkx]], [[1tkz]], [[1tl1]], [[1tl3]] - P66/P51+ quinoline derivative<br />
**[[1tkt]], [[1tkx]], [[1tkz]], [[1tl1]], [[1tl3]] - P66/P51+ quinoline derivative<br />
Line 78: Line 80:


**[[3kjv]], [[3kk3]], [[1r0a]], [[1n5y]], [[1n6q]], [[1hys]], [[5d3g]], [[5i3u]] - P66/P51+DNA<br />  
**[[3kjv]], [[3kk3]], [[1r0a]], [[1n5y]], [[1n6q]], [[1hys]], [[5d3g]], [[5i3u]] - P66/P51+DNA<br />  
**[[1j5o]], [[1rtd]], [[3klf]], [[3v4i]], [[3v6d]] - P66/P51 (mutant)+DNA<br />
**[[1j5o]], [[1rtd]], [[3klf]], [[3v4i]], [[3v6d]], [[6avt]], [[6avm]], [[6asw]], [[5j2q]], [[5j2p]], [[5j2m]] - P66/P51 (mutant)+DNA<br />
**[[4r5p]], [[5j2n]], [[5txo]], [[5txp]] - P66/P51 (mutant) + nucleotide + DNA<br />
**[[4r5p]], [[5j2n]], [[5txo]], [[5txp]] - P66/P51 (mutant) + nucleotide + DNA<br />
**[[3v81]] - P66/P51 (mutant)+DNA + NNRTI<br />
**[[3v81]] - P66/P51 (mutant)+DNA + NNRTI<br />
**[[1hvu]] - P66/P51+RNA<br />  
**[[1hvu]] - P66/P51+RNA<br />  
**[[4b3o]], [[4b3p]], [[4b3q]] - P66/P51 + RNA + DNA<br />
**[[4b3o]], [[4b3p]], [[4b3q]], [[6bsj]], [[6bsi]], [[6bsh]], [[6bsg]] - P66/P51 + RNA + DNA<br />
**[[4pqu]] - P66/P51 (mutant) + dATP + RNA + DNA<br />
**[[4pqu]] - P66/P51 (mutant) + dATP + RNA + DNA<br />
**[[5i42]] - P66/P51 + dTTP + DNA<br />
**[[6anq]], [[6an8]], [[6an2]], [[6amo]] - P66/P51 (mutant) + dTTP + DNA<br />
**[[5txn]], [[5txm]], [[5txl]] - P66/P51 (mutant) + dATP + DNA<br />
**[[6b19]] - P66/P51 (mutant) + tRNA + RNA<br />
**[[4puo]], [[4pwd]], [[4q0b]] - P66/P51 (mutant) + nevirapine + RNA + DNA<br />
**[[4puo]], [[4pwd]], [[4q0b]] - P66/P51 (mutant) + nevirapine + RNA + DNA<br />
**[[1t03]], [[1t05]] - P66/P51+DNA+Fab+NRTI<br />
**[[1t03]], [[1t05]] - P66/P51+DNA+Fab+NRTI<br />
Line 104: Line 110:
**[[5t82]] - P66 thumb domain - NMR<br />
**[[5t82]] - P66 thumb domain - NMR<br />


*RT/ribonuclease H domain or Hiv-1 P15
*Hiv-1 P15


**[[4mh8]] – MmlvRT P80<br />
**[[4m94]], [[4m95]] – MmlvRT P80 catalytic fragment + DNA<br />
**[[4ifv]] – Hiv1P66/P55 (mutant) <br />
**[[2ykm]], [[2ykn]] – Hiv1P66 (mutant) + NNRTI <br />
**[[4qag]] – Hiv1P66 + coumarin derivative <br />
**[[4h4m]] – Hiv1P66/P55 (mutant) + NNRTI <br />
**[[4h4o]], [[4rw4]], [[4rw6]], [[4rw7]], [[4rw8]], [[4rw9]] – Hiv1P66/P51 (mutant) + NNRTI <br />
**[[2ynh]], [[2yni]], [[4ncg]] – Hiv1P66/P51 + NNRTI <br />
**[[1rdh]], [[1hrh]], [[5dzm]] – P15<br />
**[[1rdh]], [[1hrh]], [[5dzm]] – P15<br />
**[[3lp3]] – P15+inhibitor MK3<br />
**[[3lp3]] – P15+inhibitor MK3<br />
Line 126: Line 124:
* Moloney murine leukemia virus reverse transcriptase  
* Moloney murine leukemia virus reverse transcriptase  


**[[1mml]] - MmlvRT residues 130-194<br />
**[[1mml]] - MmlvRT residues 130-394<br />
**[[2hb5]] – MmlvRT RNAse domain residues 618-791<br />
**[[4mh8]] – MmlvRT P80 residues 683-1330<br />
**[[2hb5]] - MmlvRT residues 618-791<br />
**[[2hb5]] - MmlvRT residues 618-791<br />
**[[1nnd]] - MmlvRT catalytic domain (mutant)<br />
**[[1nnd]] - MmlvRT catalytic domain (mutant)<br />
**[[2r2r]], [[2r2t]], [[2fjv]], [[2fjw]], [[2fjx]], [[1ztw]], [[2fvs]], [[2fvr]], [[2fvq]], [[2fvp]], [[1n4l]], [[4xo0]], [[4xpc]], [[4xpe]] – MmlvRT catalytic domain +DNA<br />
**[[2r2r]], [[2r2t]], [[2fjv]], [[2fjw]], [[2fjx]], [[1ztw]], [[2fvs]], [[2fvr]], [[2fvq]], [[2fvp]], [[1n4l]], [[4xo0]], [[4xpc]], [[4xpe]], [[5vbs]], [[4m94]], [[4m95]] – MmlvRT catalytic domain + DNA<br />
**[[2r2s]], [[2r2u]] - MmlvRT catalytic domain +DNA+Co Bleomycin<br />
**[[2r2s]], [[2r2u]] - MmlvRT catalytic domain +DNA+Co Bleomycin<br />
**[[1ztt]] - MmlvRT catalytic domain +DNA+netropsin<br />
**[[1ztt]] - MmlvRT catalytic domain +DNA+netropsin<br />
Line 138: Line 138:
**[[5dmq]], [[5dmr]] - MmlvRT + ERF1<br />
**[[5dmq]], [[5dmr]] - MmlvRT + ERF1<br />


*XMRV reverse transcriptase
*Xenotropic mulv-related virus reverse transcriptase


**[[3v1o]], [[3v1q]] – RNAse H domain<br />
**[[3v1o]], [[3v1q]] – RNAse H domain<br />
**[[3v1r]] – RNAse H domain + inhibitor<br />
**[[3v1r]] – RNAse H domain + inhibitor<br />
**[[4hkq]] – RT residues 658-1328 (mutant) + DNA + RNA<br />
**[[4hkq]] – RT residues 658-1328 (mutant) + DNA + RNA<br />
**[[2lsn]] – RT – Simian foamy virus - NMR


*Reverse transcriptase from telomerase
*Reverse transcriptase from telomerase
Line 150: Line 148:
**[[2b2a]] - TtRT telomerase catalytic subunit (mutant) - ''Tetrahymena thermophila''<br />
**[[2b2a]] - TtRT telomerase catalytic subunit (mutant) - ''Tetrahymena thermophila''<br />
**[[2r4g]] - TtRT telomerase catalytic subunit<br />
**[[2r4g]] - TtRT telomerase catalytic subunit<br />
**[[6d6v]] – TtRT + telomerase-associated protein + TEB2 + RNA + DNA – Cryo EM<br />
**[[5c9h]] - TtRT catalytic subunit + DNA<br />
**[[5c9h]] - TtRT catalytic subunit + DNA<br />
**[[3du6]], [[3du5]] - TcRT telomerase catalytic subunit - ''Tribolium castaneum''<br />
**[[3du6]], [[3du5]] - TcRT telomerase catalytic subunit - ''Tribolium castaneum''<br />
Line 158: Line 157:
**[[5ugw]] - hRT thumb domain<br />
**[[5ugw]] - hRT thumb domain<br />
**[[5cqg]] - RT + inhibitor - red flour beetle<br />
**[[5cqg]] - RT + inhibitor - red flour beetle<br />
**[[5npt]] – RT N-terminal – ''Ogataea polymorpha''<br />
*other RT
**[[2lsn]] – RT – Simian foamy virus – NMR<br />
**[[4ol8]] - P55 (mutant) + RNA + DNA - yeast<br />


}}
}}