 |
PDBsum entry 3f2d
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transferase/DNA
|
PDB id
|
|
|
|
3f2d
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure of polc reveals unique DNA binding and fidelity determinants.
|
|
|
Authors
|
|
R.J.Evans,
D.R.Davies,
J.M.Bullard,
J.Christensen,
L.S.Green,
J.W.Guiles,
J.D.Pata,
W.K.Ribble,
N.Janjic,
T.C.Jarvis.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 2008,
105,
20695-20700.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
PolC is the polymerase responsible for genome duplication in many Gram-positive
bacteria and represents an attractive target for antibacterial development. We
have determined the 2.4-A resolution crystal structure of Geobacillus
kaustophilus PolC in a ternary complex with DNA and dGTP. The structure reveals
nascent base pair interactions that lead to highly accurate nucleotide
incorporation. A unique beta-strand motif in the PolC thumb domain contacts the
minor groove, allowing replication errors to be sensed up to 8 nt upstream of
the active site. PolC exhibits the potential for large-scale conformational
flexibility, which could encompass the catalytic residues. The structure
suggests a mechanism by which the active site can communicate with the rest of
the replisome to trigger proofreading after nucleotide misincorporation, leading
to an integrated model for controlling the dynamic switch between replicative
and repair polymerases. This ternary complex of a cellular replicative
polymerase affords insights into polymerase fidelity, evolution, and structural
diversity.
|
|
|
|
|
|
|
|
Figure 2.
PHP β-barrel architecture. Schematic representations are
shown of canonical PHP (αβ)[7]-barrel (Left) (see Fig. S3),
the PolC PHP domain (Center), and the TaqDnaE PHP domain [Right,
based on Protein Data Bank (PDB) ID code 2HPI]. Red circles
indicate the locations of metal-chelating residues. Filled red
circles indicate the locations of metal-chelating residues that
are conserved between PolC and TaqDnaE, open circles indicate
the locations of metal-chelating residues in PolC and TaqDnaE
that are not conserved in EcoDnaE.
|
|
Figure 4.
Comparison of polymerase active sites from the β-NT and
classical superfamilies. The active sites and DNA substrates are
shown from PolC (colored as in Fig. 1) and TaqDnaE (white; PDB
ID code 3E0D) C family polymerases (A), Polβ (PDB ID code
2FMP), an X family polymerase (B), and RB69 (PDB ID code 1IG9),
a B family polymerase (C). (B and C) Palms are colored magenta,
and fingers are colored blue.
|
|
|
|
|
|
|
|
|
|
