 |
PDBsum entry 3a46
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Structural characterization of a viral neil1 ortholog unliganded and bound to abasic site-Containing DNA.
|
|
|
Authors
|
|
K.Imamura,
S.S.Wallace,
S.Doublié.
|
|
|
Ref.
|
|
J Biol Chem, 2009,
284,
26174-26183.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
Endonuclease VIII (Nei) is a DNA glycosylase of the base excision repair pathway
that recognizes and excises oxidized pyrimidines. We determined the crystal
structures of a NEIL1 ortholog from the giant Mimivirus (MvNei1) unliganded and
bound to DNA containing tetrahydrofuran (THF), which is the first structure of
any Nei with an abasic site analog. The MvNei1 structures exhibit the same
overall architecture as other enzymes of the Fpg/Nei family, which consists of
two globular domains joined by a linker region. MvNei1 harbors a zincless
finger, first described in human NEIL1, rather than the signature zinc finger
generally found in the Fpg/Nei family. In contrast to Escherichia coli Nei,
where a dramatic conformational change was observed upon binding DNA, the
structure of MvNei1 bound to DNA does not reveal any substantial movement
compared with the unliganded enzyme. A protein segment encompassing residues
217-245 in MvNei1 corresponds to the "missing loop" in E. coli Nei and the
"alphaF-beta10 loop" in E. coli Fpg, which has been reported to be involved in
lesion recognition. Interestingly, the corresponding loop in MvNei1 is ordered
in both the unliganded and furan-bound structures, unlike other Fpg/Nei enzymes
where the loop is generally ordered in the unliganded enzyme or in complexes
with a lesion, and disordered otherwise. In the MvNei1.tetrahydrofuran complex a
tyrosine located at the tip of the putative lesion recognition loop stacks
against the furan ring; the tyrosine is predicted to adopt a different
conformation to accommodate a modified base.
|
|
|
|
|
|
|
|
Figure 2.
A, MvNei1·THF complex structure. The zincless finger,
H2TH, catalytic proline and glutamic acid, and conserved
arginine are highlighted in pink. The DNA is shown in gray. The
putative lesion binding loop is shown in dark green. B,
schematics of MvNei1·DNA interactions. Nucleotides are
numbered beginning from THF0, with positive numbers toward the
5′-end. Hydrogen bonds are represented with black arrows
pointing toward the acceptors. Tyr-221 stacks with THF.
|
|
Figure 3.
A, close-up view of THF and interacting residues with
overlaid simulated annealing omit map contoured at 5 σ (lime
green). MvNei1 is shown in green and DNA in gray. Hydrogen bonds
are represented by black dashed lines. B, superposition of the
MvNei1·THF complex onto LlaFpg·AP site complexes
(THF and Pr). The MvNei1·THF complex is shown in green,
LlaFpg/Pr complex (PDB code 1PJI (52)) in beige, and the
LlaFpg·THF complex (PDB code 1PM5 (52)) in orange. The
hydrogen bond is shown as a black dashed line. The blue dashed
line indicates the distance between the amino group of Pro-2 and
C1′ of THF.
|
|
|
|
|
|
The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2009,
284,
26174-26183)
copyright 2009.
|
|
|
|
|
|
|
