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PDBsum entry 1okb

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
1okb
Jmol
Contents
Protein chains
223 a.a. *
Ligands
GOL ×2
Metals
_CL ×2
Waters ×343
* Residue conservation analysis
PDB id:
1okb
Name: Hydrolase
Title: Crystal structure of uracil-DNA glycosylase from atlantic cod (gadus morhua)
Structure: Uracil-DNA glycosylase. Chain: a, b. Fragment: catalytic domain, residues 79-301. Engineered: yes. Mutation: yes
Source: Gadus morhua. Atlantic cod. Organism_taxid: 8049. Organ: liver. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.9Å     R-factor:   0.186     R-free:   0.205
Authors: I.Leiros,E.Moe,O.Lanes,A.O.Smalas,N.P.Willassen
Key ref:
I.Leiros et al. (2003). The structure of uracil-DNA glycosylase from Atlantic cod (Gadus morhua) reveals cold-adaptation features. Acta Crystallogr D Biol Crystallogr, 59, 1357-1365. PubMed id: 12876336 DOI: 10.1107/S0907444903011144
Date:
21-Jul-03     Release date:   05-Apr-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9I983  (Q9I983_GADMO) -  Uracil-DNA glycosylase
Seq:
Struc:
301 a.a.
223 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.2.2.27  - Uracil-DNA glycosylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     DNA repair   2 terms 
  Biochemical function     hydrolase activity, hydrolyzing N-glycosyl compounds     2 terms  

 

 
DOI no: 10.1107/S0907444903011144 Acta Crystallogr D Biol Crystallogr 59:1357-1365 (2003)
PubMed id: 12876336  
 
 
The structure of uracil-DNA glycosylase from Atlantic cod (Gadus morhua) reveals cold-adaptation features.
I.Leiros, E.Moe, O.Lanes, A.O.Smalås, N.P.Willassen.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
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.
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] ).
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2003, 59, 1357-1365) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18196298 M.Olufsen, A.O.Smalås, and B.O.Brandsdal (2008).
Electrostatic interactions play an essential role in DNA repair and cold-adaptation of Uracil DNA glycosylase.
  J Mol Model, 14, 201-213.  
18004790 M.Olufsen, E.Papaleo, A.O.Smalås, and B.O.Brandsdal (2008).
Ion pairs and their role in modulating stability of cold- and warm-active uracil DNA glycosylase.
  Proteins, 71, 1219-1230.  
16756497 K.S.Siddiqui, and R.Cavicchioli (2006).
Cold-adapted enzymes.
  Annu Rev Biochem, 75, 403-433.  
15670163 J.Arnórsdóttir, M.M.Kristjánsson, and R.Ficner (2005).
Crystal structure of a subtilisin-like serine proteinase from a psychrotrophic Vibrio species reveals structural aspects of cold adaptation.
  FEBS J, 272, 832-845.
PDB codes: 1s2n 1sh7
15749696 M.Olufsen, A.O.Smalås, E.Moe, and B.O.Brandsdal (2005).
Increased flexibility as a strategy for cold adaptation: a comparative molecular dynamics study of cold- and warm-active uracil DNA glycosylase.
  J Biol Chem, 280, 18042-18048.  
  16233714 A.Hoyoux, V.Blaise, T.Collins, S.D'Amico, E.Gratia, A.L.Huston, J.C.Marx, G.Sonan, Y.Zeng, G.Feller, and C.Gerday (2004).
Extreme catalysts from low-temperature environments.
  J Biosci Bioeng, 98, 317-330.  
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 codes are shown on the right.