Last stop on the road to repair: Structure of E. coli DNA ligase bound to nicked DNA-adenylate Journal Article
| Authors: | Nandakumar, J.; Nair, P. A.; Shuman, S. |
| Article Title: | Last stop on the road to repair: Structure of E. coli DNA ligase bound to nicked DNA-adenylate |
| Abstract: | NAD+-dependent DNA ligases (LigA) are ubiquitous in bacteria and essential for growth. Their distinctive substrate specificity and domain organization vis-a-vis human ATP-dependent ligases make them outstanding targets for anti-infective drug discovery. We report here the 2.3 Å crystal structure of Escherichia coli LigA bound to an adenylylated nick, which captures LigA in a state poised for strand closure and reveals the basis for nick recognition. LigA envelops the DNA within a protein clamp. Large protein domain movements and remodeling of the active site orchestrate progression through the three chemical steps of the ligation reaction. The structure inspires a strategy for inhibitor design. © 2007 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; nonhuman; protein conformation; dna repair; dna; species specificity; escherichia coli; base sequence; dna breaks, single-stranded; models, molecular; crystallography, x-ray; protein structure, tertiary; nucleic acid conformation; polydeoxyribonucleotide synthase; enzyme specificity; enzyme structure; catalytic domain; dna, bacterial; dna nick translation; enzyme synthesis; escherichia coli proteins; nicotinamide adenine dinucleotide; dna ligases; enzyme active site; adenylation; nucleotidyltransferase; liga; dna conformation; adenine nucleotides |
| Journal Title: | Molecular Cell |
| Volume: | 26 |
| Issue: | 2 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2007-04-27 |
| Start Page: | 257 |
| End Page: | 271 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2007.02.026 |
| PUBMED: | 17466627 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 26" - "Export Date: 17 November 2011" - "CODEN: MOCEF" - "Source: Scopus" |
