Structure of bacterial LigD 3'-phosphoesterase unveils a DNA repair superfamily

Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):12822-7. doi: 10.1073/pnas.1005830107. Epub 2010 Jun 29.

Abstract

The DNA ligase D (LigD) 3'-phosphoesterase (PE) module is a conserved component of the bacterial nonhomologous end-joining (NHEJ) apparatus that performs 3' end-healing reactions at DNA double-strand breaks. Here we report the 1.9 A crystal structure of Pseudomonas aeruginosa PE, which reveals that PE exemplifies a unique class of DNA repair enzyme. PE has a distinctive fold in which an eight stranded beta barrel with a hydrophobic interior supports a crescent-shaped hydrophilic active site on its outer surface. Six essential side chains coordinate manganese and a sulfate mimetic of the scissile phosphate. The PE active site and mechanism are unique vis à vis other end-healing enzymes. We find PE homologs in archaeal and eukaryal proteomes, signifying that PEs comprise a DNA repair superfamily.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Archaea / enzymology
  • Biocatalysis
  • Catalytic Domain
  • Crystallography, X-Ray
  • DNA Ligases / chemistry*
  • DNA Ligases / metabolism
  • DNA Repair Enzymes / chemistry
  • DNA Repair Enzymes / metabolism
  • DNA Repair*
  • Esterases / chemistry*
  • Esterases / metabolism
  • Eukaryota / enzymology
  • Molecular Sequence Data
  • Multigene Family*
  • Protein Structure, Tertiary
  • Pseudomonas aeruginosa / enzymology*

Substances

  • Esterases
  • DNA Ligases
  • DNA Repair Enzymes

Associated data

  • PDB/3N9B
  • PDB/3N9D