1vs0
From Proteopedia
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'''Crystal Structure of the Ligase Domain from M. tuberculosis LigD at 2.4A''' | '''Crystal Structure of the Ligase Domain from M. tuberculosis LigD at 2.4A''' | ||
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[[Category: Shuman, S.]] | [[Category: Shuman, S.]] | ||
[[Category: TBSGC, TB Structural Genomics Consortium.]] | [[Category: TBSGC, TB Structural Genomics Consortium.]] | ||
| - | [[Category: | + | [[Category: Ligase]] |
| - | [[Category: | + | [[Category: Nucleotidyl transferase]] |
| - | [[Category: | + | [[Category: Ob fold]] |
| - | [[Category: | + | [[Category: Protein structure initiative]] |
| - | [[Category: | + | [[Category: Psi]] |
| - | [[Category: | + | [[Category: Structural genomic]] |
| - | [[Category: | + | [[Category: Tb structural genomics consortium]] |
| - | [[Category: | + | [[Category: Tbsgc]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 12:51:19 2008'' | |
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Revision as of 09:51, 3 May 2008
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 Sat May 3 12:51:19 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
