2ZHX

Crystal structure of Uracil-DNA Glycosylase from Mycobacterium tuberculosis in complex with a proteinaceous inhibitor

Summary for 2ZHX

• Entry DOI: 10.2210/pdb2zhx/pdb
• Descriptor: Uracil-DNA glycosylase, Uracil-DNA glycosylase inhibitor (3 entities in total)
• Functional Keywords: dna repair, ung-ugi complex, ung-dna interactions, dna damage, glycosidase, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Mycobacterium tuberculosis H37Rv; More
• Total number of polymer chains: 14
• Total formula weight: 247073.52

Authors

Kaushal, P.S.,Talawar, R.K.,Krishna, P.D.V.,Varshney, U.,Vijayan, M. (deposition date: 2008-02-11, release date: 2008-05-20, Last modification date: 2023-11-01)

Primary citation

Kaushal, P.S.,Talawar, R.K.,Krishna, P.D.V.,Varshney, U.,Vijayan, M.
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 Crystallogr.,Sect.D, 64:551-560, 2008

PubMed 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.

PubMed: 18453691
DOI: 10.1107/S090744490800512X

Experimental method

X-RAY DIFFRACTION (3.1 Å)