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1vs0
From Proteopedia
| |||||||
| , resolution 2.400Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||
| Gene: | Rv0938, MT0965 (Mycobacterium tuberculosis) | ||||||
| Domains: | ligC, DNA_ligase_A_C, DNA_ligase_A_M | ||||||
| Resources: | FirstGlance, OCA, PDBsum, JenaLib, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
Page seeded by OCA on Wed Mar 26 06:10:09 2008
Categories: Mycobacterium tuberculosis | Single protein | Akey, D. | Aniukwu, J. | Berger, J M. | Glickman, M S. | Martins, A. | Shuman, S. | TBSGC, TB Structural Genomics Consortium. | Ligase | Nucleotidyl transferase | Ob fold | Protein structure initiative | Psi | Structural genomic | Tb structural genomics consortium | Tbsgc
