DB code: S00016

CATH domain 1.10.440.10 : Endonuclease V Catalytic domain
E.C. 3.1.25.1
CSA 1vas
M-CSA 1vas
MACiE M0162

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P04418 Endonuclease V
EC 3.1.25.1
NP_049733.1 (Protein)
NC_000866.4 (DNA/RNA sequence)
PF03013 (Pyr_excise)
[Graphical View]

KEGG enzyme name
deoxyribonuclease (pyrimidine dimer)
endodeoxyribonuclease (pyrimidine dimer)
endodeoxyribonuclease (pyrimidine dimer)
bacteriophage T4 endodeoxyribonuclease V
T4 endonuclease V

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P04418 END5_BPT4 Endonucleolytic cleavage near pyrimidine dimers to products with 5''-phosphate. Monomer.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id L00011 C00001 C00578 L00013
E.C.
Compound cys-syn pyrimidine dimer in DNA H2O DNA 5'-phosphate DNA 3'-trans-alpha,beta unsaturated aldehyde
Type nucleic acids H2O nucleic acids,phosphate group/phosphate ion nucleic acids,carbohydrate
ChEBI 15377
 15377
PubChem 22247451
 962
 22247451
 962
1endA Unbound Unbound Unbound
1eniA Unbound Unbound Unbound
1enjA Unbound Unbound Unbound
1enkA Unbound Unbound Unbound
1vasA Bound:A-T-C-G-C-G-T-T-G-C-G-C-T (chain B) Unbound Unbound
2endA Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P04418 & literature [20]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1endA GLU 23;ARG 26 THR 2
1eniA GLU 23;ARG 26 THR 2
1enjA ;ARG 26 THR 2 mutant E23Q
1enkA ;ARG 26 THR 2 mutant E23D
1vasA ;ARG 26 THR 2 mutant E23Q
2endA GLU 23;ARG 26 THR 2

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig. 1, p.51-54
[6]
Scheme 1, p.17637-17638
[9]
Fig.1
[10]
Fig.1, p.9424
[11]
p.524-525
[12]
Fig.1
[14]
Fig.8, p.182-193
[15]
Fig.1, p.201-205
[17]
Fig.1
[18]
Fig.4, p.778-779
[19]
Fig.1, p.2660-2661
[20]
p.369-371
[21]
[23]
Fig.1, p.32152
[25]
p.258-261

References
[1]
Resource
Comments
Medline ID
PubMed ID 3172233
Journal J Mol Biol
Year 1988
Volume 202
Pages 683-4
Authors Morikawa K, Tsujimoto M, Ikehara M, Inaoka T, Ohtsuka E
Title Preliminary crystallographic study of pyrimidine dimer-specific excision-repair enzyme from bacteriophage T4.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2671706
Journal Mutat Res
Year 1989
Volume 218
Pages 49-65
Authors Dodson ML, Lloyd RS
Title Structure-function studies of the T4 endonuclease V repair enzyme.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 2695926
Journal Proteins
Year 1989
Volume 6
Pages 128-38
Authors Lloyd RS, Augustine ML
Title Site-directed mutagenesis of the T4 endonuclease V gene: mutations which enhance enzyme specific activity at low salt concentrations.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1888726
Journal Biochemistry
Year 1991
Volume 30
Pages 8638-48
Authors Nickell C, Lloyd RS
Title Mutations in endonuclease V that affect both protein-protein association and target site location.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 2037608
Journal J Biol Chem
Year 1991
Volume 266
Pages 10686-93
Authors Prince MA, Friedman B, Gruskin EA, Schrock RD 3rd, Lloyd RS
Title Selective metal binding to Cys-78 within endonuclease V causes an inhibition of catalytic activities without altering nontarget and target DNA binding.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 1894643
Journal J Biol Chem
Year 1991
Volume 266
Pages 17631-9
Authors Schrock RD 3rd, Lloyd RS
Title Reductive methylation of the amino terminus of endonuclease V eradicates catalytic activities. Evidence for an essential role of the amino terminus in the chemical mechanisms of catalysis.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 2067549
Journal Mutat Res
Year 1991
Volume 255
Pages 19-29
Authors Dodson ML, Prince MA, Anderson WF, Lloyd RS
Title Site-directed deletion mutagenesis within the T4 endonuclease V gene: dispensable sequences within putative loop regions.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 1841278
Journal Nucleic Acids Symp Ser
Year 1991
Volume 4
Pages 181-4
Authors Morikawa K, Matsumoto O, Tsujimoto M, Katayanagi K, Doi T, Ariyoshi M, Ikehara M, Inaoka T, Ohtsuka E
Title Atomic structure of a pyrimidine-dimer specific excision-repair enzyme from bacteriophage T4.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 1357629
Journal Nucleic Acids Res
Year 1992
Volume 20
Pages 4761-4
Authors Hori N, Doi T, Karaki Y, Kikuchi M, Ikehara M, Ohtsuka E
Title Participation of glutamic acid 23 of T4 endonuclease V in the beta-elimination reaction of an abasic site in a synthetic duplex DNA.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 1409651
Journal Proc Natl Acad Sci U S A
Year 1992
Volume 89
Pages 9420-4
Authors Doi T, Recktenwald A, Karaki Y, Kikuchi M, Morikawa K, Ikehara M, Inaoka T, Hori N, Ohtsuka E
Title Role of the basic amino acid cluster and Glu-23 in pyrimidine dimer glycosylase activity of T4 endonuclease V.
Related PDB
Related UniProtKB
[11]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
Medline ID
PubMed ID 1575827
Journal Science
Year 1992
Volume 256
Pages 523-6
Authors Morikawa K, Matsumoto O, Tsujimoto M, Katayanagi K, Ariyoshi M, Doi T, Ikehara M, Inaoka T, Ohtsuka E
Title X-ray structure of T4 endonuclease V: an excision repair enzyme specific for a pyrimidine dimer.
Related PDB
Related UniProtKB P04418
[12]
Resource
Comments
Medline ID
PubMed ID 8347626
Journal Biochemistry
Year 1993
Volume 32
Pages 8284-90
Authors Dodson ML, Schrock RD 3rd, Lloyd RS
Title Evidence for an imino intermediate in the T4 endonuclease V reaction.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 8441681
Journal Nucleic Acids Res
Year 1993
Volume 21
Pages 727-32
Authors Green AP, deRiel JK, Henderson EE
Title Structure/function analysis of the Ala116-->Lys121 region of endonuclease V by random targeted mutagenesis.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 7916555
Journal Ann N Y Acad Sci
Year 1994
Volume 26
Pages 181-96
Authors Latham KA, Lloyd RS
Title T4 endonuclease V. Perspectives on catalysis.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8092676
Journal Ann N Y Acad Sci
Year 1994
Volume 26
Pages 198-207
Authors Morikawa K, Ariyoshi M, Vassylyev D, Katayanagi K, Nakamura H, Doi T, Hori N, Ohtsuka E
Title Crystal structure of T4 endonuclease V. An excision repair enzyme for a pyrimidine dimer.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 8286363
Journal Biochemistry
Year 1994
Volume 33
Pages 57-64
Authors Lee BJ, Sakashita H, Ohkubo T, Ikehara M, Doi T, Morikawa K, Kyogoku Y, Osafune T, Iwai S, Ohtsuka E
Title Nuclear magnetic resonance study of the interaction of T4 endonuclease V with DNA.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 7718562
Journal Biochemistry
Year 1995
Volume 34
Pages 4601-9
Authors Iwai S, Maeda M, Shirai M, Shimada Y, Osafune T, Murata T, Ohtsuka E
Title Reaction mechanism of T4 endonuclease V determined by analysis using modified oligonucleotide duplexes.
Related PDB
Related UniProtKB
[18]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8521494
Journal Cell
Year 1995
Volume 83
Pages 773-82
Authors Vassylyev DG, Kashiwagi T, Mikami Y, Ariyoshi M, Iwai S, Ohtsuka E, Morikawa K
Title Atomic model of a pyrimidine dimer excision repair enzyme complexed with a DNA substrate: structural basis for damaged DNA recognition.
Related PDB 1vas
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 7852333
Journal J Biol Chem
Year 1995
Volume 270
Pages 2652-61
Authors Manuel RC, Latham KA, Dodson ML, Lloyd RS
Title Involvement of glutamic acid 23 in the catalytic mechanism of T4 endonuclease V.
Related PDB
Related UniProtKB
[20]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 7783199
Journal J Mol Biol
Year 1995
Volume 249
Pages 360-75
Authors Morikawa K, Ariyoshi M, Vassylyev DG, Matsumoto O, Katayanagi K, Ohtsuka E
Title Crystal structure of a pyrimidine dimer-specific excision repair enzyme from bacteriophage T4: refinement at 1.45 A and X-ray analysis of the three active site mutants.
Related PDB 1end 1eni 1enj 1enk 2end
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 8943268
Journal J Biol Chem
Year 1996
Volume 271
Pages 32147-52
Authors McCullough AK, Scharer O, Verdine GL, Lloyd RS
Title Structural determinants for specific recognition by T4 endonuclease V.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 9100001
Journal Biochemistry
Year 1997
Volume 36
Pages 4080-8
Authors Nyaga SG, Dodson ML, Lloyd RS
Title Role of specific amino acid residues in T4 endonuclease V that alter nontarget DNA binding.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 9341165
Journal J Biol Chem
Year 1997
Volume 272
Pages 27210-7
Authors McCullough AK, Dodson ML, Scharer OD, Lloyd RS
Title The role of base flipping in damage recognition and catalysis by T4 endonuclease V.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 9582353
Journal J Biol Chem
Year 1998
Volume 273
Pages 13136-42
Authors McCullough AK, Romberg MT, Nyaga S, Wei Y, Wood TG, Taylor JS, Van Etten JL, Dodson ML, Lloyd RS
Title Characterization of a novel cis-syn and trans-syn-II pyrimidine dimer glycosylase/AP lyase from a eukaryotic algal virus, Paramecium bursaria chlorella virus-1.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 10946233
Journal Mutat Res
Year 2000
Volume 460
Pages 257-75
Authors Morikawa K, Shirakawa M
Title Three-dimensional structural views of damaged-DNA recognition: T4 endonuclease V, E. coli Vsr protein, and human nucleotide excision repair factor XPA.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 11265291
Journal Methods Mol Biol
Year 2001
Volume 60
Pages 3-14
Authors Lloyd RS
Title Processivity of DNA repair enzymes.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 12783877
Journal J Biol Chem
Year 2003
Volume 278
Pages 30985-92
Authors Ahn HC, Ohkubo T, Iwai S, Morikawa K, Lee BJ
Title Interaction of T4 endonuclease V with DNA: importance of the flexible loop regions in protein-DNA interaction.
Related PDB
Related UniProtKB

Comments
Although this enzyme classified into hydrolase (E.C. 3.-.-.-), it does not catalyzes hydrolysis. According to the literature [18], [19], [20], [23] & [25], this enzyme catalyzes the following reactions succesively, although the detailed mechanism has not been elucidated.
(I) glycosylase reaction to form Schiff-base intermediate.
(A) Transfer of deoxyribose group from pyrimidine dimer to the N-terminal alpha-amino group.
(B) Eliminative double-bond formation; Ring opening of deoxyribose, forming Schiff-base intermediate.
(II) AP lyase reaction.
(C) Isomerization; Shift of double-bond from Schiff-base to adjacent bond.
(D) Eliminative double-bond formation; beta-elimination of 3'-phosphate from the opened deoxyribose group.
(E) Exchange of double-bonded atoms; Schiff-base deformation (hydration)
####
The N-terminal alpha-amino group of Thr2 forms Schiff-base with C1' atom of the deoxyribose. Glu23 seems to be required for both reactions, (I) & (II).

Created Updated
2004-03-19 2009-02-26