1vs0 | pdb_00001vs0

File:1vs0.gif

spinqualitylabelsall models 1vs0, resolution 2.400Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

Crystal Structure of the Ligase Domain from M. tuberculosis LigD at 2.4A

Overview

DNA ligase D (LigD) is a large polyfunctional enzyme involved in, nonhomologous end-joining (NHEJ) in mycobacteria. LigD consists of a, C-terminal ATP-dependent ligase domain fused to upstream polymerase and, phosphoesterase modules. Here we report the 2.4 angstroms crystal, structure of the ligase domain of Mycobacterium LigD, captured as the, covalent ligase-AMP intermediate with a divalent metal in the active site., A chloride anion on the protein surface coordinated by the ribose 3'-OH, and caged by arginine and lysine side chains is a putative mimetic of the, 5'-phosphate at a DNA nick. Structure-guided mutational analysis revealed, distinct requirements for the adenylylation and end-sealing reactions, catalyzed by LigD. We found that a mutation of Mycobacterium LigD that, ablates only ligase activity results in decreased fidelity of NHEJ in vivo, and a strong bias of mutagenic events toward deletions instead of, insertions at the sealed DNA ends. This phenotype contrasts with the, increased fidelity of double-strand break repair in deltaligD cells or in, a strain in which only the polymerase function of LigD is defective. We, surmise that the signature error-prone quality of bacterial NHEJ in vivo, arises from a dynamic balance between the end-remodeling and end-sealing, steps.

About this Structure

1VS0 is a Single protein structure of sequence from Mycobacterium tuberculosis with ZN, CL and MG as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure and nonhomologous end-joining function of the ligase component of Mycobacterium DNA ligase D., Akey D, Martins A, Aniukwu J, Glickman MS, Shuman S, Berger JM, J Biol Chem. 2006 May 12;281(19):13412-23. Epub 2006 Feb 13. PMID:16476729

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