 |
PDBsum entry 2uvw
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.2.7.7.7
- DNA-directed Dna polymerase.
|
|
|
|
|
|
|
Reaction:
|
|
DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
|
|
|
|
|
|
DNA(n)
|
+
|
2'-deoxyribonucleoside 5'-triphosphate
|
=
|
DNA(n+1)
|
+
|
diphosphate
|
|
|
|
|
|
|
|
|
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
DOI no:
|
J Biol Chem
282:19831-19843
(2007)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Hydrogen bonding of 7,8-dihydro-8-oxodeoxyguanosine with a charged residue in the little finger domain determines miscoding events in Sulfolobus solfataricus DNA polymerase Dpo4.
|
|
R.L.Eoff,
A.Irimia,
K.C.Angel,
M.Egli,
F.P.Guengerich.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) has been shown to catalyze
bypass of 7,8-dihydro-8-oxodeoxyguanosine (8-oxoG) in a highly efficient and
relatively accurate manner. Crystal structures have revealed a potential role
for Arg(332) in stabilizing the anti conformation of the 8-oxoG template base by
means of a hydrogen bond or ion-dipole pair, which results in an increased
enzymatic efficiency for dCTP insertion and makes formation of a Hoogsteen pair
between 8-oxoG and dATP less favorable. Site-directed mutagenesis was used to
replace Arg(332) with Ala, Glu, Leu, or His in order to probe the importance of
Arg(332) in accurate and efficient bypass of 8-oxoG. The double mutant
Ala(331)Ala(332) was also prepared to address the contribution of Arg(331).
Transientstate kinetic results suggest that Glu(332) retains fidelity against
bypass of 8-oxoG that is similar to wild type Dpo4, a result that was confirmed
by tandem mass spectrometric analysis of full-length extension products. A
crystal structure of the Dpo4 Glu(332) mutant and 8-oxoG:C pair revealed
water-mediated hydrogen bonds between Glu(332) and the O-8 atom of 8-oxoG. The
space normally occupied by Arg(332) side chain is empty in the crystal
structures of the Ala(332) mutant. Two other crystal structures show that a
Hoogsteen base pair is formed between 8-oxoG and A in the active site of both
Glu(332) and Ala(332) mutants. These results support the view that a bond
between Arg(332) and 8-oxoG plays a role in determining the fidelity and
efficiency of Dpo4-catalyzed bypass of the lesion.
|
|
|
|
|
|
| |
Selected figure(s)
|
|
|
|
| |
|
|
|
|
|
|
Figure 5.
Hydrogen bonding interactions between Dpo4 and the 8-oxoG
lesion.A, R332A(8-oxoG:A); B, R332A(8-oxoG:C); C,
R332E(8-oxoG:A); D, R332E(8-oxoG:C); E, wild type 8-oxoG:dATP;
F, wild type 8-oxoG:dCTP. The protein is shown with schematic
α-helices and β-strands. The DNA duplex and selected Dpo4
residues are shown in stick mode. Ca^2+ ions and water molecules
are shown as yellow and red spheres, respectively, and hydrogen
bonds as dashed lines.
|
|
Figure 7.
Superposition of the little finger domains of wild type Dpo4
andS. cerevisiae Pol η. Dpo4 and Pol η (Protein Data Bank
accession code 1jih (44)) are represented schematically with
secondary structure elements colored blue and red, respectively.
The positions of the Cα atoms of Arg^332 (Dpo4) and Lys^498
(Pol η) are shown as spheres.
|
|
|
|
|
|
| |
The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
19831-19843)
copyright 2007.
|
|
| |
Figures were
selected
by an automated process.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
K.N.Kirouac,
and
H.Ling
(2011).
Unique active site promotes error-free replication opposite an 8-oxo-guanine lesion by human DNA polymerase iota.
|
| |
Proc Natl Acad Sci U S A,
108,
3210-3215.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
H.Zhang,
and
F.P.Guengerich
(2010).
Effect of N2-guanyl modifications on early steps in catalysis of polymerization by Sulfolobus solfataricus P2 DNA polymerase Dpo4 T239W.
|
| |
J Mol Biol,
395,
1007-1018.
|
|
|
|
|
|
|
J.D.Pata
(2010).
Structural diversity of the Y-family DNA polymerases.
|
| |
Biochim Biophys Acta,
1804,
1124-1135.
|
|
|
|
|
|
|
L.Maddukuri,
R.L.Eoff,
J.Y.Choi,
C.J.Rizzo,
F.P.Guengerich,
and
L.J.Marnett
(2010).
In vitro bypass of the major malondialdehyde- and base propenal-derived DNA adduct by human Y-family DNA polymerases κ, ι, and Rev1.
|
| |
Biochemistry,
49,
8415-8424.
|
|
|
|
|
|
|
P.Raychaudhury,
and
A.K.Basu
(2010).
Replication Past the γ-Radiation-Induced Guanine-Thymine Cross-Link G[8,5-Me]T by Human and Yeast DNA Polymerase η.
|
| |
J Nucleic Acids,
2010,
0.
|
|
|
|
|
|
|
R.L.Eoff,
J.Y.Choi,
and
F.P.Guengerich
(2010).
Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage.
|
| |
J Nucleic Acids,
2010,
0.
|
|
|
|
|
|
|
T.D.Silverstein,
R.Jain,
R.E.Johnson,
L.Prakash,
S.Prakash,
and
A.K.Aggarwal
(2010).
Structural basis for error-free replication of oxidatively damaged DNA by yeast DNA polymerase η.
|
| |
Structure,
18,
1463-1470.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
A.Irimia,
R.L.Eoff,
F.P.Guengerich,
and
M.Egli
(2009).
Structural and functional elucidation of the mechanism promoting error-prone synthesis by human DNA polymerase kappa opposite the 7,8-dihydro-8-oxo-2'-deoxyguanosine adduct.
|
| |
J Biol Chem,
284,
22467-22480.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
H.Zhang,
R.L.Eoff,
I.D.Kozekov,
C.J.Rizzo,
M.Egli,
and
F.P.Guengerich
(2009).
Versatility of Y-family Sulfolobus solfataricus DNA polymerase Dpo4 in translesion synthesis past bulky N2-alkylguanine adducts.
|
| |
J Biol Chem,
284,
3563-3576.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
H.Zhang,
R.L.Eoff,
I.D.Kozekov,
C.J.Rizzo,
M.Egli,
and
F.P.Guengerich
(2009).
Structure-function relationships in miscoding by Sulfolobus solfataricus DNA polymerase Dpo4: guanine N2,N2-dimethyl substitution produces inactive and miscoding polymerase complexes.
|
| |
J Biol Chem,
284,
17687-17699.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
O.Rechkoblit,
L.Malinina,
Y.Cheng,
N.E.Geacintov,
S.Broyde,
and
D.J.Patel
(2009).
Impact of conformational heterogeneity of OxoG lesions and their pairing partners on bypass fidelity by Y family polymerases.
|
| |
Structure,
17,
725-736.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
P.P.Christov,
K.C.Angel,
F.P.Guengerich,
and
C.J.Rizzo
(2009).
Replication past the N5-methyl-formamidopyrimidine lesion of deoxyguanosine by DNA polymerases and an improved procedure for sequence analysis of in vitro bypass products by mass spectrometry.
|
| |
Chem Res Toxicol,
22,
1086-1095.
|
|
|
|
|
|
|
P.Xu,
L.Oum,
Y.C.Lee,
N.E.Geacintov,
and
S.Broyde
(2009).
Visualizing sequence-governed nucleotide selectivities and mutagenic consequences through a replicative cycle: processing of a bulky carcinogen N2-dG lesion in a Y-family DNA polymerase.
|
| |
Biochemistry,
48,
4677-4690.
|
|
|
|
|
|
|
R.L.Eoff,
J.B.Stafford,
J.Szekely,
C.J.Rizzo,
M.Egli,
F.P.Guengerich,
and
L.J.Marnett
(2009).
Structural and functional analysis of Sulfolobus solfataricus Y-family DNA polymerase Dpo4-catalyzed bypass of the malondialdehyde-deoxyguanosine adduct.
|
| |
Biochemistry,
48,
7079-7088.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
R.L.Eoff,
R.Sanchez-Ponce,
and
F.P.Guengerich
(2009).
Conformational changes during nucleotide selection by Sulfolobus solfataricus DNA polymerase Dpo4.
|
| |
J Biol Chem,
284,
21090-21099.
|
|
|
|
|
|
|
S.Schneider,
S.Schorr,
and
T.Carell
(2009).
Crystal structure analysis of DNA lesion repair and tolerance mechanisms.
|
| |
Curr Opin Struct Biol,
19,
87-95.
|
|
|
|
|
|
|
J.C.Delaney,
and
J.M.Essigmann
(2008).
Biological properties of single chemical-DNA adducts: a twenty year perspective.
|
| |
Chem Res Toxicol,
21,
232-252.
|
|
|
|
|
|
|
J.W.Beckman,
Q.Wang,
and
F.P.Guengerich
(2008).
Kinetic analysis of correct nucleotide insertion by a Y-family DNA polymerase reveals conformational changes both prior to and following phosphodiester bond formation as detected by tryptophan fluorescence.
|
| |
J Biol Chem,
283,
36711-36723.
|
|
|
|
|
|
|
J.Y.Choi,
and
F.P.Guengerich
(2008).
Kinetic analysis of translesion synthesis opposite bulky N2- and O6-alkylguanine DNA adducts by human DNA polymerase REV1.
|
| |
J Biol Chem,
283,
23645-23655.
|
|
|
|
|
|
|
S.Broyde,
L.Wang,
O.Rechkoblit,
N.E.Geacintov,
and
D.J.Patel
(2008).
Lesion processing: high-fidelity versus lesion-bypass DNA polymerases.
|
| |
Trends Biochem Sci,
33,
209-219.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
|
|
Links
