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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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cytoplasm
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1 term
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Biological process
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response to DNA damage stimulus
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4 terms
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Biochemical function
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nucleotide binding
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8 terms
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DOI no:
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Proc Natl Acad Sci U S A
96:11717-11722
(1999)
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PubMed id:
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Crystal structure of the DNA nucleotide excision repair enzyme UvrB from Thermus thermophilus.
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M.Machius,
L.Henry,
M.Palnitkar,
J.Deisenhofer.
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ABSTRACT
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Nucleotide excision repair (NER) is the most important DNA-repair mechanism in
living organisms. In prokaryotes, three enzymes forming the UvrABC system
initiate NER of a variety of structurally different DNA lesions. UvrB, the
central component of this system, is responsible for the ultimate DNA damage
recognition and participates in the incision of the damaged DNA strand. The
crystal structure of Thermus thermophilus UvrB reveals a core that is
structurally similar to core regions found in helicases, where they constitute
molecular motors. Additional domains implicated in binding to DNA and various
components of the NER system are attached to this central core. The architecture
and distribution of DNA binding sites suggest a possible model for the DNA
damage recognition process.
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Selected figure(s)
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Figure 1.
Fig. 1. Single isomorphous replacement/anomalous
scattering electron density (green) contoured at 2.0 after
density modification with the final model superimposed. Shown is
the core of helicase domain H2. Carbon atoms are in gray, oxygen
atoms in red, nitrogen atoms in blue, and sulfur atoms in yellow.
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Figure 2.
Fig. 2. (A) Overall topology of Tt UvrB. Domains not
visible in the electron density are indicated by blue circles.
(B) Functional sites in UvrB. Figs. 1, 2, and 3 were made with
BOBSCRIPT (53), GRASP (54), POV-RAY (Persistence of Vision
Raytracer, v3.02, POV-Team, www.povray.org), and GL_RENDER (L.
Esser, University of Texas Southwestern Medical Center at
Dallas).
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.Jaciuk,
E.Nowak,
K.Skowronek,
A.Tańska,
and
M.Nowotny
(2011).
Structure of UvrA nucleotide excision repair protein in complex with modified DNA.
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Nat Struct Mol Biol, 18,
191-197.
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PDB code:
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N.M.Kad,
H.Wang,
G.G.Kennedy,
D.M.Warshaw,
and
B.Van Houten
(2010).
Collaborative dynamic DNA scanning by nucleotide excision repair proteins investigated by single- molecule imaging of quantum-dot-labeled proteins.
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Mol Cell, 37,
702-713.
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R.Morita,
S.Nakane,
A.Shimada,
M.Inoue,
H.Iino,
T.Wakamatsu,
K.Fukui,
N.Nakagawa,
R.Masui,
and
S.Kuramitsu
(2010).
Molecular mechanisms of the whole DNA repair system: a comparison of bacterial and eukaryotic systems.
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J Nucleic Acids, 2010,
179594.
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L.Manelyte,
C.P.Guy,
R.M.Smith,
M.S.Dillingham,
P.McGlynn,
and
N.J.Savery
(2009).
The unstructured C-terminal extension of UvrD interacts with UvrB, but is dispensable for nucleotide excision repair.
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DNA Repair (Amst), 8,
1300-1310.
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N.T.Uyen,
S.Y.Park,
J.W.Choi,
H.J.Lee,
K.Nishi,
and
J.S.Kim
(2009).
The fragment structure of a putative HsdR subunit of a type I restriction enzyme from Vibrio vulnificus YJ016: implications for DNA restriction and translocation activity.
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Nucleic Acids Res, 37,
6960-6969.
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PDB code:
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D.L.Croteau,
M.J.DellaVecchia,
L.Perera,
and
B.Van Houten
(2008).
Cooperative damage recognition by UvrA and UvrB: identification of UvrA residues that mediate DNA binding.
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DNA Repair (Amst), 7,
392-404.
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D.Pakotiprapha,
Y.Inuzuka,
B.R.Bowman,
G.F.Moolenaar,
N.Goosen,
D.Jeruzalmi,
and
G.L.Verdine
(2008).
Crystal structure of Bacillus stearothermophilus UvrA provides insight into ATP-modulated dimerization, UvrB interaction, and DNA binding.
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Mol Cell, 29,
122-133.
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PDB code:
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E.J.Enemark,
and
L.Joshua-Tor
(2008).
On helicases and other motor proteins.
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Curr Opin Struct Biol, 18,
243-257.
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M.J.DellaVecchia,
W.K.Merritt,
Y.Peng,
T.W.Kirby,
E.F.DeRose,
G.A.Mueller,
B.Van Houten,
and
R.E.London
(2007).
NMR analysis of [methyl-13C]methionine UvrB from Bacillus caldotenax reveals UvrB-domain 4 heterodimer formation in solution.
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J Mol Biol, 373,
282-295.
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N.J.Savery
(2007).
The molecular mechanism of transcription-coupled DNA repair.
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Trends Microbiol, 15,
326-333.
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J.J.Truglio,
E.Karakas,
B.Rhau,
H.Wang,
M.J.DellaVecchia,
B.Van Houten,
and
C.Kisker
(2006).
Structural basis for DNA recognition and processing by UvrB.
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Nat Struct Mol Biol, 13,
360-364.
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PDB code:
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N.H.Thomä,
B.K.Czyzewski,
A.A.Alexeev,
A.V.Mazin,
S.C.Kowalczykowski,
and
N.P.Pavletich
(2005).
Structure of the SWI2/SNF2 chromatin-remodeling domain of eukaryotic Rad54.
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Nat Struct Mol Biol, 12,
350-356.
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PDB code:
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S.Rocak,
B.Emery,
N.K.Tanner,
and
P.Linder
(2005).
Characterization of the ATPase and unwinding activities of the yeast DEAD-box protein Has1p and the analysis of the roles of the conserved motifs.
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Nucleic Acids Res, 33,
999.
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H.Ma,
and
Y.Zou
(2004).
Thermodynamic characterization of the interaction of mutant UvrB protein with damaged DNA.
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Biochemistry, 43,
4206-4211.
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H.Shi,
O.Cordin,
C.M.Minder,
P.Linder,
and
R.M.Xu
(2004).
Crystal structure of the human ATP-dependent splicing and export factor UAP56.
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Proc Natl Acad Sci U S A, 101,
17628-17633.
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PDB codes:
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J.J.Truglio,
D.L.Croteau,
M.Skorvaga,
M.J.DellaVecchia,
K.Theis,
B.S.Mandavilli,
B.Van Houten,
and
C.Kisker
(2004).
Interactions between UvrA and UvrB: the role of UvrB's domain 2 in nucleotide excision repair.
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EMBO J, 23,
2498-2509.
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PDB code:
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M.Kampmann,
and
D.Stock
(2004).
Reverse gyrase has heat-protective DNA chaperone activity independent of supercoiling.
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Nucleic Acids Res, 32,
3537-3545.
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P.L.Garcia,
G.Bradley,
C.J.Hayes,
S.Krintel,
P.Soultanas,
and
P.Janscak
(2004).
RPA alleviates the inhibitory effect of vinylphosphonate internucleotide linkages on DNA unwinding by BLM and WRN helicases.
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Nucleic Acids Res, 32,
3771-3778.
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Y.Zou,
H.Ma,
I.G.Minko,
S.M.Shell,
Z.Yang,
Y.Qu,
Y.Xu,
N.E.Geacintov,
and
R.S.Lloyd
(2004).
DNA damage recognition of mutated forms of UvrB proteins in nucleotide excision repair.
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Biochemistry, 43,
4196-4205.
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M.D.Betterton,
and
F.Jülicher
(2003).
A motor that makes its own track: helicase unwinding of DNA.
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Phys Rev Lett, 91,
258103.
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M.L.Quillin,
and
B.W.Matthews
(2003).
Selling candles in a post-Edison world: phasing with noble gases bound within engineered sites.
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Acta Crystallogr D Biol Crystallogr, 59,
1930-1934.
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M.Machius
(2003).
Structural biology: a high-tech tool for biomedical research.
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Curr Opin Nephrol Hypertens, 12,
431-438.
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Y.Zou,
S.M.Shell,
C.D.Utzat,
C.Luo,
Z.Yang,
N.E.Geacintov,
and
A.K.Basu
(2003).
Effects of DNA adduct structure and sequence context on strand opening of repair intermediates and incision by UvrABC nuclease.
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Biochemistry, 42,
12654-12661.
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A.C.Rodríguez,
and
D.Stock
(2002).
Crystal structure of reverse gyrase: insights into the positive supercoiling of DNA.
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EMBO J, 21,
418-426.
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PDB codes:
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E.E.Verhoeven,
C.Wyman,
G.F.Moolenaar,
and
N.Goosen
(2002).
The presence of two UvrB subunits in the UvrAB complex ensures damage detection in both DNA strands.
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EMBO J, 21,
4196-4205.
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I.G.Minko,
Y.Zou,
and
R.S.Lloyd
(2002).
Incision of DNA-protein crosslinks by UvrABC nuclease suggests a potential repair pathway involving nucleotide excision repair.
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Proc Natl Acad Sci U S A, 99,
1905-1909.
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J.M.Caruthers,
and
D.B.McKay
(2002).
Helicase structure and mechanism.
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Curr Opin Struct Biol, 12,
123-133.
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M.R.Singleton,
and
D.B.Wigley
(2002).
Modularity and specialization in superfamily 1 and 2 helicases.
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J Bacteriol, 184,
1819-1826.
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A.Cohen,
P.Ellis,
N.Kresge,
and
S.M.Soltis
(2001).
MAD phasing with krypton.
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Acta Crystallogr D Biol Crystallogr, 57,
233-238.
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E.E.Verhoeven,
C.Wyman,
G.F.Moolenaar,
J.H.Hoeijmakers,
and
N.Goosen
(2001).
Architecture of nucleotide excision repair complexes: DNA is wrapped by UvrB before and after damage recognition.
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EMBO J, 20,
601-611.
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G.F.Moolenaar,
L.Höglund,
and
N.Goosen
(2001).
Clue to damage recognition by UvrB: residues in the beta-hairpin structure prevent binding to non-damaged DNA.
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EMBO J, 20,
6140-6149.
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M.R.Singleton,
S.Scaife,
and
D.B.Wigley
(2001).
Structural analysis of DNA replication fork reversal by RecG.
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Cell, 107,
79-89.
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PDB code:
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R.Soliva,
V.Monaco,
I.Gómez-Pinto,
N.J.Meeuwenoord,
G.A.Marel,
J.H.Boom,
C.González,
and
M.Orozco
(2001).
Solution structure of a DNA duplex with a chiral alkyl phosphonate moiety.
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Nucleic Acids Res, 29,
2973-2985.
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PDB codes:
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X.Yu,
S.A.Jacobs,
S.C.West,
T.Ogawa,
and
E.H.Egelman
(2001).
Domain structure and dynamics in the helical filaments formed by RecA and Rad51 on DNA.
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Proc Natl Acad Sci U S A, 98,
8419-8424.
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E.C.Friedberg
(2000).
Biological responses to DNA damage: a perspective in the new millennium.
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Cold Spring Harb Symp Quant Biol, 65,
593-602.
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J.M.Caruthers,
E.R.Johnson,
and
D.B.McKay
(2000).
Crystal structure of yeast initiation factor 4A, a DEAD-box RNA helicase.
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Proc Natl Acad Sci U S A, 97,
13080-13085.
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PDB codes:
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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
code is
shown on the right.
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