EzCatDB: M00206
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DB codeM00206
RLCP classification1.13.200.966 : Hydrolysis
CATH domainDomain 1-.-.-.-
Domain 22.40.70.10 : Cathepsin D, subunit A; domain 1Catalytic domain
Domain 33.10.10.10 : HIV Type 1 Reverse Transcriptase; Chain A, domain 1
Domain 43.30.70.270 : Alpha-Beta Plaits
Domain 53.30.70.270 : Alpha-Beta Plaits
Domain 63.30.70.270 : Alpha-Beta Plaits
Domain 73.30.420.10 : Nucleotidyltransferase; domain 5
Domain 82.70.40.10 : Deoxyuridine 5'-Triphosphate Nucleotidohydrolase; Chain ACatalytic domain
Domain 91.10.10.200 : Arc Repressor Mutant, subunit A
Domain 103.30.420.10 : Nucleotidyltransferase; domain 5
Domain 112.30.30.10 : SH3 type barrels.
E.C.3.4.23.-,2.7.7.49,3.1.26.4,3.6.1.23

CATH domainRelated DB codes (homologues)
1.10.10.200 : Arc Repressor Mutant, subunit AM00166
2.30.30.10 : SH3 type barrels.M00135,M00146
2.40.70.10 : Cathepsin D, subunit A; domain 1D00471,D00436,D00438,D00439,D00440,D00441,D00442,D00443,D00437,D00444,D00423,D00445,D00484,M00166,D00231,D00529
2.70.40.10 : Deoxyuridine 5'-Triphosphate Nucleotidohydrolase; Chain AT00231
3.10.10.10 : HIV Type 1 Reverse Transcriptase; Chain A, domain 1M00135,M00146,M00166
3.30.420.10 : Nucleotidyltransferase; domain 5T00252,M00019,M00020,M00055,M00135,M00146,M00166,M00173,M00175,M00186
3.30.70.270 : Alpha-Beta PlaitsM00019,M00135,M00146,M00166,M00209

Enzyme Name
UniProtKBKEGG

P16088
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)

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)

dUTP diphosphatase
   (EC 3.6.1.23)

deoxyuridine-triphosphatase
   (EC 3.6.1.23)

dUTPase
   (EC 3.6.1.23)

dUTP pyrophosphatase
   (EC 3.6.1.23)

desoxyuridine 5'-triphosphate nucleotidohydrolase
   (EC 3.6.1.23)

desoxyuridine 5'-triphosphatase
   (EC 3.6.1.23)

SynonymsNone
ContainsProtease Retropepsin
   EC 3.4.23.-
Reverse transcriptase/ribonuclease H
(RT)
   EC 2.7.7.49
   EC 3.1.26.4
Deoxyuridine 5''-triphosphate nucleotidohydrolase
(dUTPase)
   EC 3.6.1.23
Integrase
(IN)
PfamPF00692 (dUTPase)
PF00552 (IN_DBD_C)
PF02022 (Integrase_Zn)
PF00075 (RNase_H)
PF00665 (rve)
PF00077 (RVP)
PF00078 (RVT_1)
PF06815 (RVT_connect)
PF06817 (RVT_thumb)
[Graphical view]

KEGG pathways
MAP codePathwaysE.C.
MAP00240Pyrimidine metabolism3.6.1.23

UniProtKB:Accession NumberP16088
Entry namePOL_FIVPE
ActivityEndonucleolytic cleavage to 5''- phosphomonoester.,dUTP + H(2)O = dUMP + diphosphate.,Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Subunit
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00305C00017C00012C00677C00039C00046C00460C00001C00017C00012C00039C00960C00365C00013I00136
E.C.
3.4.23.-3.4.23.-2.7.7.492.7.7.493.1.26.43.6.1.233.4.23.-,3.1.26.4,3.6.1.233.4.23.-3.4.23.-2.7.7.493.1.26.43.6.1.232.7.7.49,3.6.1.233.4.23.-
CompoundMagnesiumProteinPeptideDeoxynucleoside triphosphateDNA(n)RNAdUTPH2OProteinPeptideDNA(n+1)RNA 5'-phosphatedUMPPyrophosphateAmino-diol-tetrahedral intermediate
Typedivalent metal (Ca2+, Mg2+)peptide/proteinpeptide/proteinnucleotidenucleic acidsnucleic acidsamide group,nucleotideH2Opeptide/proteinpeptide/proteinnucleic acidsnucleic acids,phosphate group/phosphate ionamide group,nucleotidephosphate group/phosphate ion
ChEBI18420





17625
15377




17622
29888

PubChem888





65070
962
22247451




65063
21961011
1023

                       
1b11AUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundAnalogue:INTUnboundUnboundUnboundUnboundUnbound
1fivAUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundTransition-state-analogue:ACE-ALN-VAL-STA-GLU-ALN
2fivAUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundTransition-state-analogue:ACE-ALN-VAL-STA-GLU-ALN-NH2
3fivAUnboundUnboundAnalogue:ACE-ALN-VAL-LEU-ALA-GLU-ALN-NH2(chain I,J)UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
4fivAUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundTransition-state-analogue:LP1
5fivAUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundAnalogue:INTUnboundUnboundUnboundUnboundUnbound
6fivAUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundAnalogue:INTUnboundUnboundUnboundUnboundUnbound
2fivBUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fivBUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1dutABound:_MGUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1dutBBound:_MGUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f7dABound:_MGUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f7dBBound:_MGUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f7kABound:_MGUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundBound:UMPUnboundUnbound
1f7kBBound:_MGUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundBound:UMPUnboundUnbound
1f7nABound:_MGUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundBound:UMPUnboundUnbound
1f7nBBound:_MGUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundBound:UMPUnboundUnbound
1f7oAUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f7oBUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f7oCUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f7pAUnboundUnboundUnboundUnboundUnboundUnboundAnalogue:UDP UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f7pBUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f7pCUnboundUnboundUnboundUnboundUnboundUnboundAnalogue:UDP UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f7qAUnboundUnboundUnboundUnboundUnboundUnboundBound:DUTBound:HOH 658UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f7qBUnboundUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f7qCUnboundUnboundUnboundUnboundUnboundUnboundBound:DUTBound:HOH 646UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f7rABound:_MGUnboundUnboundUnboundUnboundUnboundAnalogue:UDP UnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P16088
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysiscomment
            
1b11AASP 30
 
 
(EC 3.4.23.-)
1fivAASP 30
 
 
(EC 3.4.23.-)
2fivA      
 
 
(EC 3.4.23.-) mutant D30N
3fivA      
 
 
(EC 3.4.23.-) mutant D30N
4fivAASP 30
 
 
(EC 3.4.23.-)
5fivAASP 30
 
 
(EC 3.4.23.-)
6fivAASP 30
 
 
(EC 3.4.23.-)
2fivB      
 
 
(EC 3.4.23.-) mutant D30N
3fivB      
 
 
(EC 3.4.23.-) mutant D30N
1dutALYS  55;ASP  71;LYS  97;GLN 100
ASP  64(magnesium binding)
SER  56;SER  57
(EC 3.6.1.23)
1dutBLYS  55;ASP  71;LYS  97;GLN 100
ASP  64(magnesium binding)
SER  56;SER  57
(EC 3.6.1.23)
1f7dALYS  55;ASP  71;LYS  97;GLN 100
ASP  64(magnesium binding)
SER  56;SER  57
(EC 3.6.1.23)
1f7dBLYS 255;ASP 271;LYS 297;GLN 300
ASP 264(magnesium binding)
SER 256;SER 257
(EC 3.6.1.23)
1f7kALYS  55;ASP  71;LYS  97;GLN 100
ASP  64(magnesium binding)
SER  56;SER  57
(EC 3.6.1.23)
1f7kBLYS 255;ASP 271;LYS 297;GLN 300
ASP 264(magnesium binding)
SER 256;SER 257
(EC 3.6.1.23)
1f7nALYS  55;ASP  71;LYS  97;GLN 100
ASP  64(magnesium binding)
SER  56;SER  57
(EC 3.6.1.23)
1f7nBLYS 255;ASP 271;LYS 297;GLN 300
ASP 264(magnesium binding)
SER 256;SER 257
(EC 3.6.1.23)
1f7oALYS  55;ASP  71;LYS  97;GLN 100
ASP  64(magnesium binding)
SER  56;SER  57
(EC 3.6.1.23)
1f7oBLYS 255;ASP 271;LYS 297;GLN 300
ASP 264(magnesium binding)
SER 256;SER 257
(EC 3.6.1.23)
1f7oCLYS 455;ASP 471;LYS 497;GLN 500
ASP 464(magnesium binding)
SER 456;SER 457
(EC 3.6.1.23)
1f7pALYS  55;ASP  71;LYS  97;GLN 100
ASP  64(magnesium binding)
SER  56;SER  57
(EC 3.6.1.23)
1f7pBLYS 255;ASP 271;LYS 297;GLN 300
ASP 264(magnesium binding)
SER 256;SER 257
(EC 3.6.1.23)
1f7pCLYS 455;ASP 471;LYS 497;GLN 500
ASP 464(magnesium binding)
SER 456;SER 457
(EC 3.6.1.23)
1f7qALYS  55;ASP  71;LYS  97;GLN 100
ASP  64(magnesium binding)
SER  56;SER  57
(EC 3.6.1.23)
1f7qBLYS 255;ASP 271;LYS 297;GLN 300
ASP 264(magnesium binding)
SER 256;SER 257
(EC 3.6.1.23)
1f7qCLYS 455;ASP 471;LYS 497;GLN 500
ASP 464(magnesium binding)
SER 456;SER 457
(EC 3.6.1.23)
1f7rALYS  55;ASP  71;LYS  97;GLN 100
ASP  64(magnesium binding)
SER  56;SER  57
(EC 3.6.1.23)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Fig.1
[4]Fig.8, p.10705-10707

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 42-154. Retropepsin (3.4.23.-)
Medline ID95393228
PubMed ID7664111
JournalNat Struct Biol
Year1995
Volume2
Pages480-8
AuthorsWlodawer A, Gustchina A, Reshetnikova L, Lubkowski J, Zdanov A, Hui KY, Angleton EL, Farmerie WG, Goodenow MM, Bhatt D, et al
TitleStructure of an inhibitor complex of the proteinase from feline immunodeficiency virus.
Related PDB1fiv
Related UniProtKBP16088
[2]
CommentsRetropepsin (3.4.23.-)
PubMed ID9022971
JournalBioorg Med Chem
Year1996
Volume4
Pages2055-69
AuthorsQian X, Moris-Varas F, Fitzgerald MC, Wong CH
TitleC2-symmetrical tetrahydroxyazepanes as inhibitors of glycosidases and HIV/FIV proteases.
[3]
CommentsdUTP pyrophosphatase (3.6.1.23)
PubMed ID8976551
JournalProtein Sci
Year1996
Volume5
Pages2429-37
AuthorsPrasad GS, Stura EA, McRee DE, Laco GS, Hasselkus-Light C, Elder JH, Stout CD
TitleCrystal structure of dUTP pyrophosphatase from feline immunodeficiency virus.
Related PDB1dut
[4]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 42-154. Retropepsin (3.4.23.-)
Medline ID97419133
PubMed ID9271500
JournalBiochemistry
Year1997
Volume36
Pages10696-708
AuthorsLaco GS, Schalk-Hihi C, Lubkowski J, Morris G, Zdanov A, Olson A, Elder JH, Wlodawer A, Gustchina A
TitleCrystal structures of the inactive D30N mutant of feline immunodeficiency virus protease complexed with a substrate and an inhibitor.
Related PDB2fiv,3fiv
Related UniProtKBP16088
[5]
CommentsX-ray crystallography. Retropepsin (3.4.23.-)
PubMed ID9827997
JournalProtein Sci
Year1998
Volume7
Pages2314-23
AuthorsKervinen J, Lubkowski J, Zdanov A, Bhatt D, Dunn BM, Hui KY, Powell DJ, Kay J, Wlodawer A, Gustchina A
TitleToward a universal inhibitor of retroviral proteases: comparative analysis of the interactions of LP-130 complexed with proteases from HIV-1, FIV, and EIAV.
Related PDB4fiv
[6]
CommentsRetropepsin (3.4.23.-)
PubMed ID10380354
JournalBiopolymers
Year1999
Volume51
Pages69-77
AuthorsDunn BM, Pennington MW, Frase DC, Nash K
TitleComparison of inhibitor binding to feline and human immunodeficiency virus proteases: structure-based drug design and the resistance problem.
[7]
CommentsRetropepsin (3.4.23.-)
PubMed ID10409825
JournalProteins
Year1999
Volume36
Pages318-31
AuthorsDominy BN, Brooks CL 3rd
TitleMethodology for protein-ligand binding studies: application to a model for drug resistance, the HIV/FIV protease system.
[8]
CommentsdUTP pyrophosphatase (3.6.1.23)
PubMed ID10329142
JournalJ Mol Biol
Year1999
Volume288
Pages275-87
AuthorsHarris JM, McIntosh EM, Muscat GE
TitleStructure/function analysis of a dUTPase: catalytic mechanism of a potential chemotherapeutic target.
[9]
CommentsX-ray crystallography. Retropepsin (3.4.23.-)
PubMed ID10651036
JournalProteins
Year2000
Volume38
Pages29-40
AuthorsLi M, Morris GM, Lee T, Laco GS, Wong CH, Olson AJ, Elder JH, Wlodawer A, Gustchina A
TitleStructural studies of FIV and HIV-1 proteases complexed with an efficient inhibitor of FIV protease.
Related PDB1b11,5fiv,6fiv
[10]
CommentsdUTP pyrophosphatase (3.6.1.23)
PubMed ID10957629
JournalActa Crystallogr D Biol Crystallogr
Year2000
Volume56
Pages1100-9
AuthorsPrasad GS, Stura EA, Elder JH, Stout CD
TitleStructures of feline immunodeficiency virus dUTP pyrophosphatase and its nucleotide complexes in three crystal forms.
Related PDB1f7d,1f7k,1f7n,1f7o,1f7p,1f7q,1f7r
[11]
CommentsRetropepsin (3.4.23.-)
PubMed ID11206463
JournalBioorg Med Chem Lett
Year2001
Volume11
Pages219-22
AuthorsMak CC, Le VD, Lin YC, Elder JH, Wong CH
TitleDesign, synthesis, and biological evaluation of HIV/FIV protease inhibitors incorporating a conformationally constrained macrocycle with a small P3' residue.
[12]
CommentsRetropepsin (3.4.23.-)
PubMed ID12767979
JournalJ Virol
Year2003
Volume77
Pages6589-600
AuthorsLin YC, Beck Z, Morris GM, Olson AJ, Elder JH
TitleStructural basis for distinctions between substrate and inhibitor specificities for feline immunodeficiency virus and human immunodeficiency virus proteases.
[13]
CommentsRetropepsin (3.4.23.-)
PubMed ID15289598
JournalProc Natl Acad Sci U S A
Year2004
Volume101
Pages11640-5
AuthorsFernandez A, Rogale K, Scott R, Scheraga HA
TitleInhibitor design by wrapping packing defects in HIV-1 proteins.
[14]
CommentsdUTP pyrophosphatase (3.6.1.23)
PubMed ID16154087
JournalStructure
Year2005
Volume13
Pages1299-310
AuthorsTarbouriech N, Buisson M, Seigneurin JM, Cusack S, Burmeister WP
TitleThe monomeric dUTPase from Epstein-Barr virus mimics trimeric dUTPases.

comments
This enzyme is composed of retropepsin (EC 3.4.23.-), RNA-directed DNA polymerase (EC 2.7.7.49), RNase H (EC 3.1.26.4), dUTP pyrophosphatase (EC 3.6.1.23), and integrase.
The tertiary structures have been solved only for retropepsin (EC 3.4.23.-) and dUTP pyrophosphatase (EC 3.6.1.23). The dUTP pyrophosphatase domain (EC 3.6.1.23) forms a trimer, which binds one Mg2+ ion (see PDB;1dut).
The domains which corresponds to protease domain (EC 3.4.23.-) belong to the peptidase family-A2.
Although this domain has a catalytic aspartic residue, it forms a homodimer with a single active site with a typical catalytic dyad, composed of two aspartic acid residues. According to the literature [4], the catalytic mechanism is very similar to that of pepsin (see D00436 in EzCatDB).

createdupdated
2004-03-192012-06-28


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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