1vs0

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Revision as of 02:58, 21 November 2007

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

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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