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PDBsum entry 1bno
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Nucleotidyltransferase (DNA-binding)
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PDB id
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1bno
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Contents |
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* Residue conservation analysis
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Enzyme class 1:
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E.C.2.7.7.7
- DNA-directed Dna polymerase.
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Reaction:
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DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
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DNA(n)
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+
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2'-deoxyribonucleoside 5'-triphosphate
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=
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DNA(n+1)
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+
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diphosphate
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Enzyme class 2:
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E.C.4.2.99.-
- ?????
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Enzyme class 3:
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E.C.4.2.99.18
- DNA-(apurinic or apyrimidinic site) lyase.
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Reaction:
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2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)- 2'-deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3- dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-phospho- 2'-deoxyribonucleoside-DNA + H+
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Biochemistry
35:6188-6200
(1996)
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PubMed id:
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Three-dimensional solution structure of the N-terminal domain of DNA polymerase beta and mapping of the ssDNA interaction interface.
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D.Liu,
R.Prasad,
S.H.Wilson,
E.F.DeRose,
G.P.Mullen.
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ABSTRACT
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DNA polymerase beta (beta-Pol) consists of an N-terminal ssDNA binding domain
with deoxyribose phosphodiesterase activity and a C-terminal domain with
nucleotidyltransferase activity. The solution structure of the cloned N-terminal
domain of beta-Pol has been determined by multidimensional heteronuclear NMR
using experimental restraints that included 1030 distances based on analysis of
NOE connectivities, 68 phi, chi 1, and chi 2 torsion angles based on analysis of
couplings, and 22 hydrogen bonds. Hydrogen bonds were assessed only within
helices by the absence of saturation transfer from water at pH 6.7, by NOEs and
JNH alpha couplings indicative of well-structured helices, and by 13C alpha
chemical shifts characteristic of helices. The root mean square deviation for
heavy backbone atoms within the helices was 0.64 A in 55 structures. The
solution structure of the N-terminal domain is formed from four helices packed
as two antiparallel pairs crossing at 50 degrees in a V-like shape. The domain
binds p(dT)8, a template analogue, as a 1:1 complex in 100 mM NaCl (KD = 10
microM). Analysis of the binding equilibria at increasing NaCl concentrations
indicated that ionic contacts contribute to the complex. The binding interaction
was mapped to one face of the domain by characterizing backbone 1H and 15N
chemical shift changes. Assigned intermolecular NOEs from 2D NOESY support the
assessment of the binding interface. The structure that forms the interaction
surface includes an antiparallel helix-3-turn-helix-4 motif and residues
adjacent to an omega-type loop connecting helix-1 and helix-2. Sites appropriate
for nucleotide contact on the structure are described. The mapped interaction
interface for a ssDNA template is the first described for a DNA polymerase.
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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.R.Gryk,
J.Vyas,
and
M.W.Maciejewski
(2010).
Biomolecular NMR data analysis.
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Prog Nucl Magn Reson Spectrosc,
56,
329-345.
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S.H.Wilson,
W.A.Beard,
D.D.Shock,
V.K.Batra,
N.A.Cavanaugh,
R.Prasad,
E.W.Hou,
Y.Liu,
K.Asagoshi,
J.K.Horton,
D.F.Stefanick,
P.S.Kedar,
M.J.Carrozza,
A.Masaoka,
and
M.L.Heacock
(2010).
Base excision repair and design of small molecule inhibitors of human DNA polymerase β.
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Cell Mol Life Sci,
67,
3633-3647.
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C.Hazan,
F.Boudsocq,
V.Gervais,
O.Saurel,
M.Ciais,
C.Cazaux,
J.Czaplicki,
and
A.Milon
(2008).
Structural insights on the pamoic acid and the 8 kDa domain of DNA polymerase beta complex: towards the design of higher-affinity inhibitors.
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BMC Struct Biol,
8,
22.
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X.Li,
J.Zhang,
Z.Cao,
J.Wu,
and
Y.Shi
(2006).
Solution structure of GOPC PDZ domain and its interaction with the C-terminal motif of neuroligin.
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Protein Sci,
15,
2149-2158.
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PDB code:
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H.Y.Hu,
J.K.Horton,
M.R.Gryk,
R.Prasad,
J.M.Naron,
D.A.Sun,
S.M.Hecht,
S.H.Wilson,
and
G.P.Mullen
(2004).
Identification of small molecule synthetic inhibitors of DNA polymerase beta by NMR chemical shift mapping.
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J Biol Chem,
279,
39736-39744.
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S.J.Kim,
W.A.Beard,
J.Harvey,
D.D.Shock,
J.R.Knutson,
and
S.H.Wilson
(2003).
Rapid segmental and subdomain motions of DNA polymerase beta.
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J Biol Chem,
278,
5072-5081.
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L.K.Zerbe,
and
R.D.Kuchta
(2002).
The p58 subunit of human DNA primase is important for primer initiation, elongation, and counting.
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Biochemistry,
41,
4891-4900.
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Y.Mizushina,
S.Kamisuki,
N.Kasai,
N.Shimazaki,
M.Takemura,
H.Asahara,
S.Linn,
S.Yoshida,
A.Matsukage,
O.Koiwai,
F.Sugawara,
H.Yoshida,
and
K.Sakaguchi
(2002).
A plant phytotoxin, solanapyrone A, is an inhibitor of DNA polymerase beta and lambda.
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J Biol Chem,
277,
630-638.
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M.J.Jezewska,
S.Rajendran,
and
W.Bujalowski
(2001).
Interactions of the 8-kDa domain of rat DNA polymerase beta with DNA.
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Biochemistry,
40,
3295-3307.
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M.W.Maciejewski,
R.Shin,
B.Pan,
A.Marintchev,
A.Denninger,
M.A.Mullen,
K.Chen,
M.R.Gryk,
and
G.P.Mullen
(2001).
Solution structure of a viral DNA repair polymerase.
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Nat Struct Biol,
8,
936-941.
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PDB code:
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L.J.Deterding,
R.Prasad,
G.P.Mullen,
S.H.Wilson,
and
K.B.Tomer
(2000).
Mapping of the 5'-2-deoxyribose-5-phosphate lyase active site in DNA polymerase beta by mass spectrometry.
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J Biol Chem,
275,
10463-10471.
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X.Shao,
and
N.V.Grishin
(2000).
Common fold in helix-hairpin-helix proteins.
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Nucleic Acids Res,
28,
2643-2650.
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Y.Mizushina,
T.Ohkubo,
F.Sugawara,
and
K.Sakaguchi
(2000).
Structure of lithocholic acid binding to the N-terminal 8-kDa domain of DNA polymerase beta.
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Biochemistry,
39,
12606-12613.
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B.W.Kirk,
and
R.D.Kuchta
(1999).
Arg304 of human DNA primase is a key contributor to catalysis and NTP binding: primase and the family X polymerases share significant sequence homology.
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Biochemistry,
38,
7727-7736.
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Y.Mizushina,
T.Ohkubo,
T.Date,
T.Yamaguchi,
M.Saneyoshi,
F.Sugawara,
and
K.Sakaguchi
(1999).
Mode analysis of a fatty acid molecule binding to the N-terminal 8-kDa domain of DNA polymerase beta. A 1:1 complex and binding surface.
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J Biol Chem,
274,
25599-25607.
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Z.Liu,
M.J.Macias,
M.J.Bottomley,
G.Stier,
J.P.Linge,
M.Nilges,
P.Bork,
and
M.Sattler
(1999).
The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins.
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Structure,
7,
1557-1566.
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PDB code:
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D.A.Connor,
A.M.Falick,
M.C.Young,
and
M.D.Shetlar
(1998).
Probing the binding region of the single-stranded DNA-binding domain of rat DNA polymerase beta using nanosecond-pulse laser-induced cross-linking and mass spectrometry.
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Photochem Photobiol,
68,
299-308.
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O.I.Lavrik,
H.P.Nasheuer,
K.Weisshart,
M.S.Wold,
R.Prasad,
W.A.Beard,
S.H.Wilson,
and
A.Favre
(1998).
Subunits of human replication protein A are crosslinked by photoreactive primers synthesized by DNA polymerases.
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Nucleic Acids Res,
26,
602-607.
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R.Prasad,
W.A.Beard,
J.Y.Chyan,
M.W.Maciejewski,
G.P.Mullen,
and
S.H.Wilson
(1998).
Functional analysis of the amino-terminal 8-kDa domain of DNA polymerase beta as revealed by site-directed mutagenesis. DNA binding and 5'-deoxyribose phosphate lyase activities.
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J Biol Chem,
273,
11121-11126.
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Y.Matsumoto,
K.Kim,
D.S.Katz,
and
J.A.Feng
(1998).
Catalytic center of DNA polymerase beta for excision of deoxyribose phosphate groups.
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Biochemistry,
37,
6456-6464.
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G.P.Mullen,
and
S.H.Wilson
(1997).
DNA polymerase beta in abasic site repair: a structurally conserved helix-hairpin-helix motif in lesion detection by base excision repair enzymes.
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Biochemistry,
36,
4713-4717.
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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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}
}
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