EzCatDB: M00135
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DB codeM00135
RLCP classification3.103.90021.1120 : Transfer
CATH domainDomain 1-.-.-.-
Domain 23.10.10.10 : HIV Type 1 Reverse Transcriptase; Chain A, domain 1
Domain 33.30.70.270 : Alpha-Beta PlaitsCatalytic domain
Domain 43.30.70.270 : Alpha-Beta Plaits
Domain 53.30.70.270 : Alpha-Beta Plaits
Domain 63.30.420.10 : Nucleotidyltransferase; domain 5Catalytic domain
Domain 7-.-.-.-
Domain 83.30.420.10 : Nucleotidyltransferase; domain 5Catalytic domain
Domain 92.30.30.10 : SH3 type barrels.
Domain 10-.-.-.-
E.C.3.4.23.-,2.7.7.49,3.1.26.4

CATH domainRelated DB codes (homologues)
2.30.30.10 : SH3 type barrels.M00206,M00146
3.10.10.10 : HIV Type 1 Reverse Transcriptase; Chain A, domain 1M00206,M00146,M00166
3.30.420.10 : Nucleotidyltransferase; domain 5M00206,T00252,M00019,M00020,M00055,M00146,M00166,M00173,M00175,M00186
3.30.70.270 : Alpha-Beta PlaitsM00206,M00019,M00146,M00166,M00209

Enzyme Name
UniProtKBKEGG

P03355
Protein nameGag-Pol polyproteinRNA-directed DNA polymerase
   (EC 2.7.7.49)

DNA nucleotidyltransferase (RNA-directed)
   (EC 2.7.7.49)

reverse transcriptase
   (EC 2.7.7.49)

revertase
   (EC 2.7.7.49)

RNA-dependent deoxyribonucleate nucleotidyltransferase
   (EC 2.7.7.49)

RNA revertase
   (EC 2.7.7.49)

RNA-dependent DNA polymerase
   (EC 2.7.7.49)

RNA-instructed DNA polymerase
   (EC 2.7.7.49)

RT
   (EC 2.7.7.49)

calf thymus ribonuclease H
   (EC 3.1.26.4)

endoribonuclease H (calf thymus)
   (EC 3.1.26.4)

RNase H
   (EC 3.1.26.4)

RNA*DNA hybrid ribonucleotidohydrolase
   (EC 3.1.26.4)

hybrid ribonuclease
   (EC 3.1.26.4)

hybridase
   (EC 3.1.26.4)

hybridase (ribonuclease H)
   (EC 3.1.26.4)

ribonuclease H
   (EC 3.1.26.4)

hybrid nuclease
   (EC 3.1.26.4)

SynonymsPr180gag-pol
ContainsMatrix protein p15
(MA)
RNA-binding phosphoprotein p12 pp12
Capsid protein p30
(CA)
Nucleocapsid protein p10
(NC-pol)
Protease p14
(PR)
   EC 3.4.23.-
Reverse transcriptase/ribonuclease H p80
(RT)
   EC 2.7.7.49
   EC 2.7.7.7
   EC 3.1.26.4
Integrase p46
(IN)
RefSeqNP_057933.2 (Protein)
NC_001501.1 (DNA/RNA sequence)
MEROPSA02.008 (Aspartic)
PfamPF01140 (Gag_MA)
PF01141 (Gag_p12)
PF02093 (Gag_p30)
PF00075 (RNase_H)
PF00665 (rve)
PF00077 (RVP)
PF00078 (RVT_1)
[Graphical view]


UniProtKB:Accession NumberP03355
Entry namePOL_MLVMO
ActivityEndonucleolytic cleavage to 5''- phosphomonoester.,Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Subunit
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC02148C00677C00039C00046C00001C00013C00039C00960
E.C.
2.7.7.492.7.7.493.1.26.43.1.26.42.7.7.492.7.7.493.1.26.4
CompoundDivalent metalDeoxynucleoside triphosphateDNA(n)RNAH2OPyrophosphateDNA(n+1)RNA 5'-phosphate
Typedivalent metal (Ca2+, Mg2+)nucleotidenucleic acidsnucleic acidsH2Ophosphate group/phosphate ionnucleic acidsnucleic acids,phosphate group/phosphate ion
ChEBI



15377
29888


PubChem



962
22247451
21961011
1023


                
1d0eA01UnboundUnboundBound:T-T-T-C-A-T-G-C-A-T-G(chain E),T-T-T-C-A-T-G-C-A-T-G(chain F)Unbound UnboundUnboundUnbound
1d0eB01UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1d1uA01UnboundUnboundBound:C-T-C-G-T-G(chain B),A-C-G-G-C-A-C-G-A-G(chain C)Unbound UnboundUnboundUnbound
1mmlA01UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1n4lA01UnboundUnboundBound:C-T-T-T-T-T-A-A-A-A-G-A-A-A-A-G(chain B),C-T-T-T-T-C-T-T-T-T-A-A-A-A-A-G(chain D)Unbound UnboundUnboundUnbound
1nndA01UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1qaiA01UnboundUnboundBound:C-A-T-G-C-A-T-G(chain D)Unbound UnboundUnboundUnbound
1qaiB01UnboundUnboundBound:C-A-T-G-C-A-T-G(chain C)Unbound UnboundUnboundUnbound
1qajA01UnboundUnboundBound:C-A-T-G-C-A-T-G(chain C),C-A-T-G-C-A-T-G(chain D)Unbound UnboundUnboundUnbound
1qajB01UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1i6jA01UnboundUnboundBound:G-T-C-G-T-C(chain B),A-C-G-G-G-A-C-G-A-C(chain C)Unbound UnboundUnboundUnbound
1zttA01UnboundUnboundBound:C-T-T-A-A-T-T-C(chain B),G-A-A-T-T-A-A-G(chain G)Unbound UnboundUnboundUnbound
1ztwA01UnboundUnboundBound:C-T-T-A-A-T-T-C(chain B),G-A-A-T-T-A-A-G(chain G)Unbound UnboundUnboundUnbound
2fjvA01UnboundUnboundBound:C-T-T-A-A-T-T-C(chain B),G-A-A-T-T-A-A-G(chain G)Unbound UnboundUnboundUnbound
2fjwA01UnboundUnboundBound:C-T-T-G-A-A-T-G(chain B),C-A-T-T-C-A-A-G(chain G)Unbound UnboundUnboundUnbound
2fjxA01UnboundUnboundBound:C-T-T-G-A-A-T-G(chain B),C-A-T-T-C-A-A-G(chain G)Unbound UnboundUnboundUnbound
1rw3A01UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1d0eA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1d0eB02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1d1uA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1mmlA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1n4lA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1nndA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1qaiA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1qaiB02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1qajA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1qajB02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1i6jA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1zttA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1ztwA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
2fjvA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
2fjwA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
2fjxA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1rw3A02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1rw3A03UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1rw3A04UnboundUnboundUnboundUnbound UnboundUnboundUnbound

Active-site residues
resource
literature [2], [3], [18]
pdbCofactor-binding residuesMain-chain involved in catalysiscomment
           
1d0eA01 
 
 
1d0eB01 
 
 
1d1uA01 
 
 
1mmlA01 
 
 
1n4lA01 
 
 
1nndA01 
 
mutant R116A
1qaiA01 
 
 
1qaiB01 
 
 
1qajA01 
 
 
1qajB01 
 
 
1i6jA01 
 
 
1zttA01 
 
 
1ztwA01 
 
 
2fjvA01 
 
 
2fjwA01 
 
 
2fjxA01 
 
 
1rw3A01 
 
 
1d0eA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1d0eB02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1d1uA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1mmlA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1n4lA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1nndA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1qaiA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1qaiB02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1qajA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1qajB02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1i6jA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1zttA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1ztwA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
2fjvA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
2fjwA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
2fjxA02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1rw3A02ASP 150;ASP 224;ASP 225(Divalent metals binding)
ASP 153;ALA 154
 
1rw3A03 
 
 
1rw3A04 
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Fig.5, p.35-36
[3]p.884-888
[4]Fig.7, p.5359
[18]Fig.1, p.14839-14841
[20]p.824-826

references
[1]
PubMed ID1370551
JournalJ Virol
Year1992
Volume66
Pages615-22
AuthorsTelesnitsky A, Blain SW, Goff SP
TitleDefects in Moloney murine leukemia virus replication caused by a reverse transcriptase mutation modeled on the structure of Escherichia coli RNase H.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 130-394.
Medline ID96097395
PubMed ID8535782
JournalStructure
Year1995
Volume3
Pages879-92
AuthorsGeorgiadis MM, Jessen SM, Ogata CM, Telesnitsky A, Goff SP, Hendrickson WA
TitleMechanistic implications from the structure of a catalytic fragment of Moloney murine leukemia virus reverse transcriptase.
Related PDB1mml
Related UniProtKBP03355
[4]
PubMed ID7537090
JournalBiochemistry
Year1995
Volume34
Pages5351-63
AuthorsPatel PH, Jacobo-Molina A, Ding J, Tantillo C, Clark AD Jr, Raag R, Nanni RG, Hughes SH, Arnold E
TitleInsights into DNA polymerization mechanisms from structure and function analysis of HIV-1 reverse transcriptase.
[5]
PubMed ID9684890
JournalProtein Sci
Year1998
Volume7
Pages1575-82
AuthorsSun D, Jessen S, Liu C, Liu X, Najmudin S, Georgiadis MM
TitleCloning, expression, and purification of a catalytic fragment of Moloney murine leukemia virus reverse transcriptase: crystallization of nucleic acid complexes.
[6]
PubMed ID9741851
JournalProteins
Year1998
Volume33
Pages135-43
AuthorsGoedken ER, Marqusee S
TitleFolding the ribonuclease H domain of Moloney murine leukemia virus reverse transcriptase requires metal binding or a short N-terminal extension.
[7]
PubMed ID10600369
JournalJ Mol Biol
Year1999
Volume294
Pages1097-113
AuthorsGao HQ, Sarafianos SG, Arnold E, Hughes SH
TitleSimilarities and differences in the RNase H activities of human immunodeficiency virus type 1 reverse transcriptase and Moloney murine leukemia virus reverse transcriptase.
[8]
PubMed ID10957631
JournalActa Crystallogr D Biol Crystallogr
Year2000
Volume56
Pages1120-31
AuthorsCote ML, Yohannan SJ, Georgiadis MM
TitleUse of an N-terminal fragment from moloney murine leukemia virus reverse transcriptase to facilitate crystallization and analysis of a pseudo-16-mer DNA molecule containing G-A mispairs.
[9]
PubMed ID10913435
JournalJ Biol Chem
Year2000
Volume275
Pages32299-309
AuthorsSchultz SJ, Zhang M, Kelleher CD, Champoux JJ
TitleAnalysis of plus-strand primer selection, removal, and reutilization by retroviral reverse transcriptases.
[10]
CommentsX-ray crystallography
PubMed ID10669612
JournalJ Mol Biol
Year2000
Volume296
Pages613-32
AuthorsNajmudin S, Cote ML, Sun D, Yohannan S, Montano SP, Gu J, Georgiadis MM
TitleCrystal structures of an N-terminal fragment from Moloney murine leukemia virus reverse transcriptase complexed with nucleic acid: functional implications for template-primer binding to the fingers domain.
Related PDB1d0e,1qai,1qaj
[11]
PubMed ID11000235
JournalJ Virol
Year2000
Volume74
Pages9629-36
AuthorsPfeiffer JK, Georgiadis MM, Telesnitsky A
TitleStructure-based moloney murine leukemia virus reverse transcriptase mutants with altered intracellular direct-repeat deletion frequencies.
[12]
PubMed ID10888659
JournalJ Virol
Year2000
Volume74
Pages7171-8
AuthorsSvarovskaia ES, Delviks KA, Hwang CK, Pathak VK
TitleStructural determinants of murine leukemia virus reverse transcriptase that affect the frequency of template switching.
[13]
PubMed ID11526315
JournalActa Crystallogr D Biol Crystallogr
Year2001
Volume57
Pages1238-50
AuthorsCote ML, Georgiadis MM
TitleStructure of a pseudo-16-mer DNA with stacked guanines and two G-A mispairs complexed with the N-terminal fragment of Moloney murine leukemia virus reverse transcriptase.
Related PDB1i6j
[14]
PubMed ID11124910
JournalJ Mol Biol
Year2001
Volume305
Pages341-59
AuthorsGu J, Villanueva RA, Snyder CS, Roth MJ, Georgiadis MM
TitleSubstitution of Asp114 or Arg116 in the fingers domain of moloney murine leukemia virus reverse transcriptase affects interactions with the template-primer resulting in decreased processivity.
[15]
PubMed ID11259203
JournalVirology
Year2001
Volume282
Pages206-13
AuthorsBoyer PL, Gao HQ, Frank P, Clark PK, Hughes SH
TitleThe basic loop of the RNase H domain of MLV RT is important both for RNase H and for polymerase activity.
[16]
PubMed ID11237609
JournalJ Mol Biol
Year2001
Volume306
Pages931-43
AuthorsWinshell J, Champoux JJ
TitleStructural alterations in the DNA ahead of the primer terminus during displacement synthesis by reverse transcriptases.
[17]
PubMed ID11433017
JournalNucleic Acids Res
Year2001
Volume29
Pages2725-32
AuthorsBerthet N, Roupioz Y, Constant JF, Kotera M, Lhomme J
TitleTranslesional synthesis on DNA templates containing the 2'-deoxyribonolactone lesion.
[18]
PubMed ID12475231
JournalBiochemistry
Year2002
Volume41
Pages14831-42
AuthorsShi Q, Singh K, Srivastava A, Kaushik N, Modak MJ
TitleLysine 152 of MuLV reverse transcriptase is required for the integrity of the active site.
[19]
CommentsX-ray crystallography
PubMed ID12818202
JournalJ Mol Biol
Year2003
Volume330
Pages57-74
AuthorsCote ML, Pflomm M, Georgiadis MM
TitleStaying straight with A-tracts: a DNA analog of the HIV-1 polypurine tract.
Related PDB1n4l
[20]
PubMed ID15130474
JournalStructure
Year2004
Volume12
Pages819-29
AuthorsDas D, Georgiadis MM
TitleThe crystal structure of the monomeric reverse transcriptase from Moloney murine leukemia virus.
Related PDB1rw3
[21]
PubMed ID16049022
JournalNucleic Acids Res
Year2005
Volume33
Pages4106-16
AuthorsGoodwin KD, Long EC, Georgiadis MM
TitleA host-guest approach for determining drug-DNA interactions: an example using netropsin.
Related PDB1ztt,1ztw
[22]
PubMed ID16771498
JournalJ Am Chem Soc
Year2006
Volume128
Pages7846-54
AuthorsGoodwin KD, Lewis MA, Tanious FA, Tidwell RR, Wilson WD, Georgiadis MM, Long EC
TitleA high-throughput, high-resolution strategy for the study of site-selective DNA binding agents: Analysis of a "highly twisted" benzimidazole-diamidine.
Related PDB2fjv,2fjw,2fjx

comments
This enzyme is composed of the N-terminal protease domain (EC 3.4.23.-), reverse transcriptase domain (E.C. 2.7.7.49), RNase H domain (3.1.26.4), and integrase domain. Only the catalytic domain of the reverse transcriptase (2.7.7.49) has been solved so far.
According to the literature [2], [3], [18], the reaction of reverse transcriptase seems to proceed as follows:
(1) 3'-hydroxyl group of DNA is activated by a magnesium ion, which is bound to Asp150 and Asp224.
(2) The activated 3'-hydroxyl group makes a nucleophilic attack on the alpha-phosphoryl group of dNTP, forming pentacovalent transition state.
(3) The transition state is stabilized by both the two magnesium ions.
(4) Stabilization by the second magnesium ion and the mainchain amide groups of Asp153 and Ala154 facilitate the leaving of beta- and gamma-phosphate groups.

createdupdated
2003-07-312009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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