title: DNA and RNA ligases: structural variations and shared mechanisms.
abstract: DNA and RNA ligases join 3' OH and 5' PO4 ends in polynucleotide substrates using a three-step reaction mechanism that involves covalent modification of both the ligase enzyme and the polynucleotide substrate with AMP. In the past three years, several polynucleotide ligases have been crystallized in complex with nucleic acid, providing the introductory views of ligase enzymes engaging their substrates. Crystal structures for two ATP-dependent DNA ligases, an NAD+-dependent DNA ligase, and an ATP-dependent RNA ligase demonstrate how ligases utilize the AMP group and their multi-domain architectures to manipulate nucleic acid structure and catalyze the end-joining reaction. Together with unliganded crystal structures of DNA and RNA ligases, a more comprehensive and dynamic understanding of the multi-step ligation reaction mechanism has emerged.
authors.affiliation: Department of Biochemistry & Molecular Biology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA. John.Pascal@mail.jci.tju.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Pascal
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D018360:Crystallography, X-Ray; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000737:chemistry* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D011130:RNA Ligase (ATP) / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D029968:Escherichia coli Proteins; D000249:Adenosine Monophosphate; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C497118:LigA protein, E coli; D011130:RNA Ligase (ATP)