Structural basis for nick recognition by a minimal pluripotent DNA ligase Journal Article


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"
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MSK Authors
  1. Mark Odell
    5 Odell
  2. Stewart H Shuman
    546 Shuman
  3. Pravin A Nair
    12 Nair
  4. Paul M C Smith
    21 Smith
  5. Christopher D Lima
    103 Lima