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PDBsum entry 3vw3
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Immune system/DNA
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PDB id
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3vw3
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References listed in PDB file
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Key reference
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Title
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Structure of a double-Stranded DNA (6-4) photoproduct in complex with the 64m-5 antibody FAB.
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Authors
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H.Yokoyama,
R.Mizutani,
Y.Satow.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2013,
69,
504-512.
[DOI no: ]
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PubMed id
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Abstract
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DNA photoproducts with (6-4) pyrimidine-pyrimidone adducts formed by ultraviolet
radiation have been implicated in mutagenesis and cancer. The crystal structure
of double-stranded DNA containing the (6-4) photoproduct in complex with the
anti-(6-4)-photoproduct antibody 64M-5 Fab was determined at 2.5 Å
resolution. The T(6-4)T segment and the 5'-side adjacent adenosine are flipped
out of the duplex and are accommodated in the concave antigen-binding pocket
composed of six complementarity-determining regions (CDRs). A loop comprised of
CDR L1 residues is inserted between the flipped-out T(6-4)T segment and the
complementary DNA. The separation of strands by the insertion of the loop
facilitates extensive and specific recognition of the photoproduct. The DNA
helices flanking the T(6-4)T segment are kinked by 87°. The 64M-5 Fab
recognizes the T(6-4)T segment dissociated from the complementary strand,
indicating that the (6-4) photoproduct can be detected in double-stranded DNA as
well as in single-stranded DNA using the 64M-5 antibody. The structure and
recognition mode of the 64M-5 antibody were compared with those of the DNA (6-4)
photolyase and nucleotide-excision repair protein DDB1-DDB2. These proteins have
distinctive binding-site structures that are appropriate for their functions,
and the flipping out of the photolesion and the kinking of the DNA are common to
mutagenic (6-4) photoproducts recognized by proteins.
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Secondary reference #1
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Title
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Structure of the DNA (6-4) photoproduct dtt(6-4)tt in complex with the 64m-2 antibody FAB fragment implies increased antibody-Binding affinity by the flanking nucleotides.
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Authors
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H.Yokoyama,
R.Mizutani,
Y.Satow,
K.Sato,
Y.Komatsu,
E.Ohtsuka,
O.Nikaido.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2012,
68,
232-238.
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PubMed id
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Secondary reference #2
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Title
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Crystal structure of the 64m-2 antibody FAB fragment in complex with a DNA dt(6-4)t photoproduct formed by ultraviolet radiation.
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Authors
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H.Yokoyama,
R.Mizutani,
Y.Satow,
Y.Komatsu,
E.Ohtsuka,
O.Nikaido.
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Ref.
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J Mol Biol, 2000,
299,
711-723.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1. Formation of DNA photoproducts by ultraviolet
irradiation. (a) Normal dTpT, (b) dT(6-4)T photodimer with the
atom numbering used, (c) cis-syn cyclobutane thymine dimer, and
(d) Dewar isomer.
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Figure 6.
Figure 6. Electrostatic representation of the 64M-2 Fab
complexed with dT(6-4)T. The electrostatic potentials are
projected onto the molecular surface of the Fab, viewed down
onto the binding site. Positive and negative potentials are
shown in blue and red, respectively. Six CDRs are indicated with
their labels. The dT(6-4)T ligand accommodated in the binding
site is drawn as a stick model. T6 and T4 represent the
5'-thymine and 3'-pyrimidone bases, respectively. O3' represents
the 3' oxygen atom (O13') of the 3'-deoxyribose. Well ordered
water molecule Wat23 is also shown as a red ball. Positive
charges are observed around the bound dT(6-4)T ligand: Arg95H
and His35H are located at the binding pocket, Lys50L and Arg54L
are possibly near the 5' side segment of elongated (6-4)
photoproducts, and Lys62H and Lys64H are possibly near the 3'
side. The Figure was produced using the program GRASP [Nicholls
et al 1991].
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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