DB code: M00146

CATH domain 3.10.10.10 : HIV Type 1 Reverse Transcriptase; Chain A, domain 1
3.30.70.270 : Alpha-Beta Plaits
1.-.-.- :
3.-.-.- :
3.30.420.10 : Nucleotidyltransferase; domain 5
-.-.-.- :
3.30.420.10 : Nucleotidyltransferase; domain 5 Catalytic domain
2.30.30.10 : SH3 type barrels.
-.-.-.- :
E.C. 2.7.7.49 2.7.7.7 3.1.26.4
CSA
M-CSA
MACiE

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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq Pfam
P03354 Pol polyprotein
None Reverse transcriptase/ribonuclease H alpha-subunit
(RT)
EC 2.7.7.49
EC 2.7.7.7
EC 3.1.26.4
Integrase
(IN)
pp32
NP_056886.1 (Protein)
NC_001407.1 (DNA/RNA sequence)
PF00607 (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 enzyme name
RNA-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 )

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P03354 POL_RSVP Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1). Endonucleolytic cleavage to 5''- phosphomonoester. The integrase forms a homotetramer. Reverse transcriptase is a heterodimer of alpha and beta subunits. Binds 8 manganese or magnesium ions per integrase homotetramer (By similarity).

KEGG Pathways
Map code Pathways E.C.
MAP00230 Purine metabolism 2.7.7.7
MAP00240 Pyrimidine metabolism 2.7.7.7

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00034 C00677 C00039 C00046 C00001 C00013 C00039 C00960
E.C. 2.7.7.49
2.7.7.7
2.7.7.49
2.7.7.7
3.1.26.4
3.1.26.4
2.7.7.49
2.7.7.7
2.7.7.49
2.7.7.7
3.1.26.4
Compound Manganese Deoxynucleoside triphosphate DNA(n) RNA H2O Pyrophosphate DNA(n+1) RNA 5'-phosphate
Type heavy metal nucleotide nucleic acids nucleic acids H2O phosphate group/phosphate ion nucleic acids nucleic acids,phosphate group/phosphate ion
ChEBI 18291
 35154
 18291
 35154
 		15377
 15377
 		29888
 29888
PubChem 23930
 23930
 		22247451
 962
 22247451
 962
 		1023
 21961011
 1023
 21961011
1c0mA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1c0mB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1c0mC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1c0mD01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1c1aA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1c1aB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a5vA Bound:_MN Unbound Unbound Unbound Unbound Unbound Unbound
1a5wA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a5xA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1asuA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1asvA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1aswA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1cxqA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1cxuA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1cz9A Unbound Unbound Unbound Unbound Analogue:SO4 Unbound Unbound
1czbA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1vsdA Analogue:_MG Unbound Unbound Unbound Unbound Unbound Unbound
1vseA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1vsfA Bound:_MN Unbound Unbound Unbound Unbound Unbound Unbound
1vshA Analogue:2x_ZN Unbound Unbound Unbound Unbound Unbound Unbound
1vsiA Analogue:_CA Unbound Unbound Unbound Unbound Unbound Unbound
1vskA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1vslA Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound
1vsmA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1c0mA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1c0mB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1c0mC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1c0mD02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1c1aA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1c1aB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [2], [9]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1c0mA01 ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1c0mB01 ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1c0mC01 ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1c0mD01 ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1c1aA01 ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1c1aB01 ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1a5vA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1a5wA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1a5xA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1asuA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1asvA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1aswA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1cxqA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1cxuA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1cz9A ;ASP 121;GLU 157(Magnesium or Manganese binding) mutant D64N
1czbA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1vsdA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1vseA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1vsfA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1vshA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1vsiA ASP 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
1vsmA ASP 64;ASP 121;GLU 157(Magnesium or Manganese binding)
1c0mA02
1c0mB02
1c0mC02
1c0mD02
1c1aA02
1c1aB02

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.339
[2]
Fig.3
[3]
[14]
Fig.9, p.12097-12098 3

References
[1]
Resource
Comments
Medline ID
PubMed ID 7563093
Journal J Mol Biol
Year 1995
Volume 253
Pages 333-46
Authors Bujacz G, Jaskolski M, Alexandratos J, Wlodawer A, Merkel G, Katz RA, Skalka AM
Title High-resolution structure of the catalytic domain of avian sarcoma virus integrase.
Related PDB 1asu 1asv 1asw
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8805516
Journal Structure
Year 1996
Volume 4
Pages 89-96
Authors Bujacz G, Jaskolski M, Alexandratos J, Wlodawer A, Merkel G, Katz RA, Skalka AM
Title The catalytic domain of avian sarcoma virus integrase: conformation of the active-site residues in the presence of divalent cations.
Related PDB 1vsd 1vse 1vsf
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9218451
Journal J Biol Chem
Year 1997
Volume 272
Pages 18161-8
Authors Bujacz G, Alexandratos J, Wlodawer A, Merkel G, Andrake M, Katz RA, Skalka AM
Title Binding of different divalent cations to the active site of avian sarcoma virus integrase and their effects on enzymatic activity.
Related PDB 1vsh 1vsi 1vsj
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9295344
Journal J Biol Chem
Year 1997
Volume 272
Pages 23938-45
Authors Vora AC, Chiu R, McCord M, Goodarzi G, Stahl SJ, Mueser TC, Hyde CC, Grandgenett DP
Title Avian retrovirus U3 and U5 DNA inverted repeats. Role Of nonsymmetrical nucleotides in promoting full-site integration by purified virion and bacterial recombinant integrases.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9560188
Journal Proc Natl Acad Sci U S A
Year 1998
Volume 95
Pages 4831-6
Authors Lubkowski J, Yang F, Alexandratos J, Wlodawer A, Zhao H, Burke TR Jr, Neamati N, Pommier Y, Merkel G, Skalka AM
Title Structure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor.
Related PDB 1a5v 1a5w 1a5x
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9830010
Journal J Biol Chem
Year 1998
Volume 273
Pages 32685-9
Authors Lubkowski J, Yang F, Alexandratos J, Merkel G, Katz RA, Gravuer K, Skalka AM, Wlodawer A
Title Structural basis for inactivating mutations and pH-dependent activity of avian sarcoma virus integrase.
Related PDB 1vsk 1vsl 1vsm
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10521258
Journal Biochemistry
Year 1999
Volume 38
Pages 13512-22
Authors Lubkowski J, Dauter Z, Yang F, Alexandratos J, Merkel G, Skalka AM, Wlodawer A
Title Atomic resolution structures of the core domain of avian sarcoma virus integrase and its D64N mutant.
Related PDB 1cxq 1cxu 1cxu 1cz9 1czb
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10384241
Journal Adv Virus Res
Year 1999
Volume 52
Pages 335-50
Authors Wlodawer A
Title Crystal structures of catalytic core domains of retroviral integrases and role of divalent cations in enzymatic activity.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10669607
Journal J Mol Biol
Year 2000
Volume 296
Pages 535-48
Authors Yang ZN, Mueser TC, Bushman FD, Hyde CC
Title Crystal structure of an active two-domain derivative of Rous sarcoma virus integrase.
Related PDB 1c0m 1c1a
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10685051
Journal Biopolymers
Year 2000
Volume 53
Pages 308-15
Authors Lins RD, Straatsma TP, Briggs JM
Title Similarities in the HIV-1 and ASV integrase active sites upon metal cofactor binding.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10961674
Journal Acta Biochim Pol
Year 2000
Volume 47
Pages 11-22
Authors Ouali M, Laboulais C, Leh H, Gill D, Xhuvani E, Zouhiri F, Desmaele D, d'Angelo J, Auclair C, Mouscadet JF, Le Bret M
Title Tautomers of styrylquinoline derivatives containing a methoxy substituent: computation of their population in aqueous solution and their interaction with RSV integrase catalytic core.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 11441016
Journal J Biol Chem
Year 2001
Volume 276
Pages 34213-20
Authors Katz RA, DiCandeloro P, Kukolj G, Skalka AM
Title Role of DNA end distortion in catalysis by avian sarcoma virus integrase.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 11024025
Journal J Biol Chem
Year 2001
Volume 276
Pages 114-24
Authors Skinner LM, Sudol M, Harper AL, Katzman M
Title Nucleophile selection for the endonuclease activities of human, ovine, and avian retroviral integrases.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 11821409
Journal J Biol Chem
Year 2002
Volume 277
Pages 12089-98
Authors Bao KK, Skalka AM, Wong I
Title Presteady-state analysis of avian sarcoma virus integrase. I. A splicing activity and structure-function implications for cognate site recognition.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 11821408
Journal J Biol Chem
Year 2002
Volume 277
Pages 12099-108
Authors Bao KK, Skalka AM, Wong I
Title Presteady-state analysis of avian sarcoma virus integrase. II. Reverse-polarity substrates identify preferential processing of the U3-U5 pair.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 12610159
Journal J Virol
Year 2003
Volume 77
Pages 3838-45
Authors Harper AL, Sudol M, Katzman M
Title An amino acid in the central catalytic domain of three retroviral integrases that affects target site selection in nonviral DNA.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 12446721
Journal J Biol Chem
Year 2003
Volume 278
Pages 1323-7
Authors Bao KK, Wang H, Miller JK, Erie DA, Skalka AM, Wong I
Title Functional oligomeric state of avian sarcoma virus integrase.
Related PDB
Related UniProtKB

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]).

Created Updated
2002-07-31 2009-03-16