Unique features of the structure and interactions of mycobacterial uracil-DNA glycosylase: structure of a complex of the Mycobacterium tuberculosis enzyme in comparison with those from other sources

Kaushal, Prem Singh ; Talawar, Ramappa K. ; Krishna, P. D. V. ; Varshney, Umesh ; Vijayan, M. (2008) Unique features of the structure and interactions of mycobacterial uracil-DNA glycosylase: structure of a complex of the Mycobacterium tuberculosis enzyme in comparison with those from other sources Acta Crystallographica Section D, 64 (5). pp. 551-560. ISSN 0907-4449

Full text not available from this repository.

Official URL: http://onlinelibrary.wiley.com/doi/10.1107/S090744...

Related URL: http://dx.doi.org/10.1107/S090744490800512X

Abstract

Uracil-DNA glycosylase (UNG), a repair enzyme involved in the excision of uracil from DNA, from mycobacteria differs from UNGs from other sources, particularly in the sequence in the catalytically important loops. The structure of the enzyme from Mycobacterium tuberculosis (MtUng) in complex with a proteinaceous inhibitor (Ugi) has been determined by X-ray analysis of a crystal containing seven crystallographically independent copies of the complex. This structure provides the first geometric characterization of a mycobacterial UNG. A comparison of the structure with those of other UNG proteins of known structure shows that a central core region of the molecule is relatively invariant in structure and sequence, while the N-and C-terminal tails exhibit high variability. The tails are probably important in folding and stability. The mycobacterial enzyme exhibits differences in UNG-Ugi interactions compared with those involving UNG from other sources. The MtUng-DNA complex modelled on the basis of the known structure of the complex involving the human enzyme indicates a domain closure in the enzyme when binding to DNA. The binding involves a larger burial of surface area than is observed in binding by human UNG. The DNA-binding site of MtUng is characterized by the presence of a higher proportion of arginyl residues than is found in the binding site of any other UNG of known structure. In addition to the electrostatic effects produced by the arginyl residues, the hydrogen bonds in which they are involved compensate for the loss of some interactions arising from changes in amino-acid residues, particularly in the catalytic loops. The results arising from the present investigation represent unique features of the structure and interaction of mycobacterial Ungs.

Item Type:Article
Source:Copyright of this article belongs to International Union of Crystallography.
Keywords:Uracil-DNA Glycosylase; Myctobacterium Tuberculosis
ID Code:56234
Deposited On:23 Aug 2011 11:57
Last Modified:15 Jul 2012 18:00

Repository Staff Only: item control page