EzCatDB: M00146
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DB codeM00146
CATH domainDomain 13.10.10.10 : HIV Type 1 Reverse Transcriptase; Chain A, domain 1
Domain 23.30.70.270 : Alpha-Beta Plaits
Domain 31.-.-.-
Domain 43.-.-.-
Domain 53.30.420.10 : Nucleotidyltransferase; domain 5
Domain 6-.-.-.-
Domain 73.30.420.10 : Nucleotidyltransferase; domain 5Catalytic domain
Domain 82.30.30.10 : SH3 type barrels.
Domain 9-.-.-.-
E.C.2.7.7.49,2.7.7.7,3.1.26.4

CATH domainRelated DB codes (homologues)
2.30.30.10 : SH3 type barrels.M00206,M00135
3.10.10.10 : HIV Type 1 Reverse Transcriptase; Chain A, domain 1M00206,M00135,M00166
3.30.420.10 : Nucleotidyltransferase; domain 5M00206,T00252,M00019,M00020,M00055,M00135,M00166,M00173,M00175,M00186
3.30.70.270 : Alpha-Beta PlaitsM00206,M00019,M00135,M00166,M00209

Enzyme Name
UniProtKBKEGG

P03354
Protein namePol 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)
DNA-directed DNA polymerase
   (EC 2.7.7.7)
DNA polymerase I
   (EC 2.7.7.7)
DNA polymerase II
   (EC 2.7.7.7)
DNA polymerase III
   (EC 2.7.7.7)
DNA polymerase alpha
   (EC 2.7.7.7)
DNA polymerase beta
   (EC 2.7.7.7)
DNA polymerase gamma
   (EC 2.7.7.7)
DNA nucleotidyltransferase (DNA-directed)
   (EC 2.7.7.7)
DNA nucleotidyltransferase (DNA-directed)
   (EC 2.7.7.7)
deoxyribonucleate nucleotidyltransferase
   (EC 2.7.7.7)
deoxynucleate polymerase
   (EC 2.7.7.7)
deoxyribonucleic acid duplicase
   (EC 2.7.7.7)
deoxyribonucleic acid polymerase
   (EC 2.7.7.7)
deoxyribonucleic duplicase
   (EC 2.7.7.7)
deoxyribonucleic polymerase
   (EC 2.7.7.7)
deoxyribonucleic polymerase I
   (EC 2.7.7.7)
DNA duplicase
   (EC 2.7.7.7)
DNA nucleotidyltransferase
   (EC 2.7.7.7)
DNA polymerase
   (EC 2.7.7.7)
DNA replicase
   (EC 2.7.7.7)
DNA-dependent DNA polymerase
   (EC 2.7.7.7)
duplicase
   (EC 2.7.7.7)
Klenow fragment
   (EC 2.7.7.7)
sequenase
   (EC 2.7.7.7)
Taq DNA polymerase
   (EC 2.7.7.7)
Taq Pol I
   (EC 2.7.7.7)
Tca DNA polymerase
   (EC 2.7.7.7)
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)
SynonymsNone
ContainsReverse transcriptase/ribonuclease H alpha-subunit
(RT)
   EC 2.7.7.49
   EC 2.7.7.7
   EC 3.1.26.4
Integrase
(IN)
pp32
RefSeqNP_056886.1 (Protein)
NC_001407.1 (DNA/RNA sequence)
PfamPF00607 (Gag_p24)
PF00552 (IN_DBD_C)
PF02022 (Integrase_Zn)
PF02813 (Retro_M)
PF00075 (RNase_H)
PF00665 (rve)
PF00077 (RVP)
PF00078 (RVT_1)
PF00098 (zf-CCHC)
[Graphical view]

KEGG pathways
MAP codePathwaysE.C.
MAP00230Purine metabolism2.7.7.7
MAP00240Pyrimidine metabolism2.7.7.7

UniProtKB:Accession NumberP03354
Entry namePOL_RSVP
ActivityDeoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).,Endonucleolytic cleavage to 5''- phosphomonoester.
SubunitThe integrase forms a homotetramer. Reverse transcriptase is a heterodimer of alpha and beta subunits.
Subcellular location
CofactorBinds 8 manganese or magnesium ions per integrase homotetramer (By similarity).

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00034C00677C00039C00046C00001C00013C00039C00960
E.C.
2.7.7.49,2.7.7.72.7.7.49,2.7.7.73.1.26.43.1.26.42.7.7.49,2.7.7.72.7.7.49,2.7.7.73.1.26.4
CompoundManganeseDeoxynucleoside triphosphateDNA(n)RNAH2OPyrophosphateDNA(n+1)RNA 5'-phosphate
Typeheavy metalnucleotidenucleic acidsnucleic acidsH2Ophosphate group/phosphate ionnucleic acidsnucleic acids,phosphate group/phosphate ion
ChEBI18291
35154



15377
29888


PubChem23930



22247451
962
1023
21961011


                
1c0mA01UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1c0mB01UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1c0mC01UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1c0mD01UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1c1aA01UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1c1aB01UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1a5vABound:_MNUnboundUnboundUnbound UnboundUnboundUnbound
1a5wAUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1a5xAUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1asuAUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1asvAUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1aswAUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1cxqAUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1cxuAUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1cz9AUnboundUnboundUnboundUnbound Analogue:SO4UnboundUnbound
1czbAUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1vsdAAnalogue:_MGUnboundUnboundUnbound UnboundUnboundUnbound
1vseAUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1vsfABound:_MNUnboundUnboundUnbound UnboundUnboundUnbound
1vshAAnalogue:2x_ZNUnboundUnboundUnbound UnboundUnboundUnbound
1vsiAAnalogue:_CAUnboundUnboundUnbound UnboundUnboundUnbound
1vskAUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1vslAAnalogue:_ZNUnboundUnboundUnbound UnboundUnboundUnbound
1vsmAUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1c0mA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1c0mB02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1c0mC02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1c0mD02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1c1aA02UnboundUnboundUnboundUnbound UnboundUnboundUnbound
1c1aB02UnboundUnboundUnboundUnbound UnboundUnboundUnbound

Active-site residues
resource
literature [2], [9]
pdbCofactor-binding residuescomment
          
1c0mA01ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1c0mB01ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1c0mC01ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1c0mD01ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1c1aA01ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1c1aB01ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1a5vAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1a5wAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1a5xAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1asuAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1asvAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1aswAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1cxqAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1cxuAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1cz9A      ;ASP 121;GLU 157(Magnesium or Manganese binding)
mutant D64N
1czbAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1vsdAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1vseAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1vsfAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1vshAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1vsiAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1vskA      ;ASP 121;GLU 157(Magnesium or Manganese binding)
mutant D64N
1vslA      ;ASP 121;GLU 157(Magnesium or Manganese binding)
mutant D64N
1vsmAASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
 
1c0mA02 
 
1c0mB02 
 
1c0mC02 
 
1c0mD02 
 
1c1aA02 
 
1c1aB02 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.339
[2]Fig.3
[3]

[14]Fig.9, p.12097-120983

references
[1]
PubMed ID7563093
JournalJ Mol Biol
Year1995
Volume253
Pages333-46
AuthorsBujacz G, Jaskolski M, Alexandratos J, Wlodawer A, Merkel G, Katz RA, Skalka AM
TitleHigh-resolution structure of the catalytic domain of avian sarcoma virus integrase.
Related PDB1asu,1asv,1asw
[2]
PubMed ID8805516
JournalStructure
Year1996
Volume4
Pages89-96
AuthorsBujacz G, Jaskolski M, Alexandratos J, Wlodawer A, Merkel G, Katz RA, Skalka AM
TitleThe catalytic domain of avian sarcoma virus integrase: conformation of the active-site residues in the presence of divalent cations.
Related PDB1vsd,1vse,1vsf
[3]
PubMed ID9218451
JournalJ Biol Chem
Year1997
Volume272
Pages18161-8
AuthorsBujacz G, Alexandratos J, Wlodawer A, Merkel G, Andrake M, Katz RA, Skalka AM
TitleBinding of different divalent cations to the active site of avian sarcoma virus integrase and their effects on enzymatic activity.
Related PDB1vsh,1vsi,1vsj
[4]
PubMed ID9295344
JournalJ Biol Chem
Year1997
Volume272
Pages23938-45
AuthorsVora AC, Chiu R, McCord M, Goodarzi G, Stahl SJ, Mueser TC, Hyde CC, Grandgenett DP
TitleAvian retrovirus U3 and U5 DNA inverted repeats. Role Of nonsymmetrical nucleotides in promoting full-site integration by purified virion and bacterial recombinant integrases.
[5]
PubMed ID9560188
JournalProc Natl Acad Sci U S A
Year1998
Volume95
Pages4831-6
AuthorsLubkowski J, Yang F, Alexandratos J, Wlodawer A, Zhao H, Burke TR Jr, Neamati N, Pommier Y, Merkel G, Skalka AM
TitleStructure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor.
Related PDB1a5v,1a5w,1a5x
[6]
PubMed ID9830010
JournalJ Biol Chem
Year1998
Volume273
Pages32685-9
AuthorsLubkowski J, Yang F, Alexandratos J, Merkel G, Katz RA, Gravuer K, Skalka AM, Wlodawer A
TitleStructural basis for inactivating mutations and pH-dependent activity of avian sarcoma virus integrase.
Related PDB1vsk,1vsl,1vsm
[7]
PubMed ID10521258
JournalBiochemistry
Year1999
Volume38
Pages13512-22
AuthorsLubkowski J, Dauter Z, Yang F, Alexandratos J, Merkel G, Skalka AM, Wlodawer A
TitleAtomic resolution structures of the core domain of avian sarcoma virus integrase and its D64N mutant.
Related PDB1cxq,1cxu,1cxu,1cz9,1czb
[8]
PubMed ID10384241
JournalAdv Virus Res
Year1999
Volume52
Pages335-50
AuthorsWlodawer A
TitleCrystal structures of catalytic core domains of retroviral integrases and role of divalent cations in enzymatic activity.
[9]
CommentsX-ray crystallography
PubMed ID10669607
JournalJ Mol Biol
Year2000
Volume296
Pages535-48
AuthorsYang ZN, Mueser TC, Bushman FD, Hyde CC
TitleCrystal structure of an active two-domain derivative of Rous sarcoma virus integrase.
Related PDB1c0m,1c1a
[10]
PubMed ID10685051
JournalBiopolymers
Year2000
Volume53
Pages308-15
AuthorsLins RD, Straatsma TP, Briggs JM
TitleSimilarities in the HIV-1 and ASV integrase active sites upon metal cofactor binding.
[11]
PubMed ID10961674
JournalActa Biochim Pol
Year2000
Volume47
Pages11-22
AuthorsOuali M, Laboulais C, Leh H, Gill D, Xhuvani E, Zouhiri F, Desmaele D, d'Angelo J, Auclair C, Mouscadet JF, Le Bret M
TitleTautomers of styrylquinoline derivatives containing a methoxy substituent: computation of their population in aqueous solution and their interaction with RSV integrase catalytic core.
[12]
PubMed ID11441016
JournalJ Biol Chem
Year2001
Volume276
Pages34213-20
AuthorsKatz RA, DiCandeloro P, Kukolj G, Skalka AM
TitleRole of DNA end distortion in catalysis by avian sarcoma virus integrase.
[13]
PubMed ID11024025
JournalJ Biol Chem
Year2001
Volume276
Pages114-24
AuthorsSkinner LM, Sudol M, Harper AL, Katzman M
TitleNucleophile selection for the endonuclease activities of human, ovine, and avian retroviral integrases.
[14]
PubMed ID11821409
JournalJ Biol Chem
Year2002
Volume277
Pages12089-98
AuthorsBao KK, Skalka AM, Wong I
TitlePresteady-state analysis of avian sarcoma virus integrase. I. A splicing activity and structure-function implications for cognate site recognition.
[15]
PubMed ID11821408
JournalJ Biol Chem
Year2002
Volume277
Pages12099-108
AuthorsBao KK, Skalka AM, Wong I
TitlePresteady-state analysis of avian sarcoma virus integrase. II. Reverse-polarity substrates identify preferential processing of the U3-U5 pair.
[16]
PubMed ID12610159
JournalJ Virol
Year2003
Volume77
Pages3838-45
AuthorsHarper AL, Sudol M, Katzman M
TitleAn amino acid in the central catalytic domain of three retroviral integrases that affects target site selection in nonviral DNA.
[17]
PubMed ID12446721
JournalJ Biol Chem
Year2003
Volume278
Pages1323-7
AuthorsBao KK, Wang H, Miller JK, Erie DA, Skalka AM, Wong I
TitleFunctional oligomeric state of avian sarcoma virus integrase.

comments
The tertiary structure of the N-terminal domains of this enzyme has not been determined yet. Only the catalytic domain of integrase has been solved so far. However, this enzyme seems to be homologous to the structures of its homologue, Pol polyprotein from Moloney murine leukemia virus (M00135 in EzCatDB), except for its N-terminal protease domain.
This enzyme catalyzes two successive reactions, hydrolysis (called processing) and transfer (called joining) (see [3]).
Although manganese is annotated as the cofactor, other divalent metal such as magnesium, cadmium and zinc can act as the cofactor (see [2] & [3]). However, in the presence of zinc ions, the polynucleotidyl transfer reaction can be inhibited, whilst the endonucleolytic reaction (hydrolysis) can be catalyzed (see [3]).

createdupdated
2002-07-312009-03-16
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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