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PDBsum entry 1okb
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The structure of uracil-Dna glycosylase from atlantic cod (gadus morhua) reveals cold-Adaptation features.
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Authors
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I.Leiros,
E.Moe,
O.Lanes,
A.O.Smalås,
N.P.Willassen.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2003,
59,
1357-1365.
[DOI no: ]
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PubMed id
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Abstract
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Uracil-DNA glycosylase (UDG; EC 3.2.2.3) is a DNA-repair protein that catalyses
the hydrolysis of promutagenic uracil residues from single- or double-stranded
DNA, generating free uracil and abasic DNA. The crystal structure of the
catalytic domain of cod uracil-DNA glycosylase (cUDG) has been determined to 1.9
A resolution, with final R factors of 18.61 and 20.57% for the working and test
sets of reflections, respectively. This is the first crystal structure of a
uracil-DNA glycosylase from a cold-adapted species and a detailed comparison
with the human enzyme is performed in order to rationalize the cold-adapted
behaviour of the cod enzyme at the structural level. The catalytic domain of
cUDG comprises 223 residues, with a sequence identity to the human UDG of 75%.
The tertiary structures of the two enzymes are also similar, with an overall
displacement in main-chain atomic positions of 0.63 A. The amino-acid
substitutions and the differences in intramolecular hydrogen bonds, hydrophobic
interactions, ion-pair interactions and electrostatic potentials are compared
and discussed in order to gain insight into the factors that cause the increased
activity and reduced thermostability of the cod enzyme. In particular, the
reduced number of strong ion-pair interactions in the C-terminal half of cUDG is
believed to greatly affect the flexibility and/or stability. Increased positive
electrostatic surface potential on the DNA-facing side of cUDG seems to be
responsible for increasing the affinity for the negatively charged DNA compared
with that of hUDG.
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Figure 1.
Figure 1 Superpositioning of the crystal structures of cUDG
(blue) and hUDG (red; PDB code [105]1akz ; Mol et al., 1995[106]
[Mol, C. D., Arvai, A. S., Slupphaug, G., Kavli, B., Alseth, I.,
Krokan, H. E. & Tainer, J. A. (1995). Cell, 80,
869-878.]-[107][bluearr.gif] ). The glycerol molecule bound in
the active site of cUDG is included for clarity.
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Figure 4.
Figure 4 Estimated electrostatic surface potentials of (a) the
crystal structure of cUDG with DNA modelled in and (b) the
crystal structure of hUDG-DNA (PDB code [145]1emh ; Parikh et
al., 2000[146] [Parikh, S. S., Walcher, G., Jones, G. D.,
Slupphaug, G., Krokan, H. E., Blackburn, G. M. & Tainer, J. A.
(2000). Proc. Natl Acad. Sci. USA, 97,
5083-5088.]-[147][bluearr.gif] ).
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2003,
59,
1357-1365)
copyright 2003.
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