Structure of bacterial LigD 3'-phosphoesterase unveils a DNA repair superfamily.
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.
Nair
Pravin A
PA
Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Smith
Paul
P
Shuman
Stewart
S
D000595:Amino Acid Sequence; D001105:Archaea / Q000201:enzymology; D055162:Biocatalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D011088:DNA Ligases / Q000737:chemistry* / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000378:metabolism; D004950:Esterases / Q000737:chemistry* / Q000378:metabolism; D056890:Eukaryota / Q000201:enzymology; D008969:Molecular Sequence Data; D005810:Multigene Family; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000201:enzymology*
D004950:Esterases; D011088:DNA Ligases; D045643:DNA Repair Enzymes