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| {{STRUCTURE_1vs0| PDB=1vs0 | SCENE= }} | | {{STRUCTURE_1vs0| PDB=1vs0 | SCENE= }} |
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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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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16476729}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16476729 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16476729}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Tb structural genomics consortium]] | | [[Category: Tb structural genomics consortium]] |
| [[Category: Tbsgc]] | | [[Category: Tbsgc]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 12:51:19 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 11:46:26 2008'' |
