Authors: | Nair, P. A.; Nandakumar, J.; Smith, P.; Odell, M.; Lima, C. D.; Shuman, S. |
Article Title: | Structural basis for nick recognition by a minimal pluripotent DNA ligase |
Abstract: | Chlorella virus DNA ligase, the smallest eukaryotic ligase known, has pluripotent biological activity and an intrinsic nick-sensing function, despite having none of the accessory domains found in cellular ligases. A 2.3-Å crystal structure of the Chlorella virus ligase-AMP intermediate bound to duplex DNA containing a 3′-OH-5′-PO4 nick reveals a new mode of DNA envelopment, in which a short surface loop emanating from the OB domain forms a Β-hairpin 'latch' that inserts into the DNA major groove flanking the nick. A network of interactions with the 3′-OH and 5′-PO 4 termini in the active site illuminates the DNA adenylylation mechanism and the crucial roles of AMP in nick sensing and catalysis. Addition of a divalent cation triggered nick sealing in crystallo, establishing that the nick complex is a bona fide intermediate in the DNA repair pathway. © 2007 Nature Publishing Group. |
Keywords: | controlled study; nonhuman; protein domain; dna repair; structure-activity relationship; eukaryota; molecular recognition; dna breaks, single-stranded; crystal structure; dna structure; models, molecular; crystallography, x-ray; protein structure, tertiary; binding sites; pluripotent stem cell; computer model; structure analysis; polydeoxyribonucleotide synthase; chlorella virus; dna ligases; viral proteins; enzyme active site; nucleotides |
Journal Title: | Nature Structural and Molecular Biology |
Volume: | 14 |
Issue: | 8 |
ISSN: | 1545-9993 |
Publisher: | Nature Publishing Group |
Date Published: | 2007-08-01 |
Start Page: | 770 |
End Page: | 778 |
Language: | English |
DOI: | 10.1038/nsmb1266 |
PUBMED: | 17618295 |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 24" - "Export Date: 17 November 2011" - "CODEN: NSMBC" - "Source: Scopus" |