title: Large serine recombinase domain structure and attachment site binding.
abstract: Large serine recombinases (LSRs) catalyze the movement of DNA elements into and out of bacterial chromosomes using site-specific recombination between short DNA "attachment sites". The LSRs that function as bacteriophage integrases carry out integration between attachment sites in the phage (attP) and in the host (attB). This process is highly directional; the reverse excision reaction between the product attL and attR sites does not occur in the absence of a phage-encoded recombination directionality factor, nor does recombination typically occur between other pairings of attachment sites. Although the mechanics of strand exchange are reasonably well understood through studies of the closely related resolvase and invertase serine recombinases, many of the fundamental aspects of the LSR reactions have until recently remained poorly understood on a structural level. In this review, we discuss the results of several years worth of biochemical and molecular genetic studies of LSRs in light of recently described structural models of LSR-DNA complexes. The focus is understanding LSR domain structure, how LSRs bind to the attP and attB attachment sites, and the differences between attP-binding and attB-binding modes. The simplicity, site-selectivity and strong directionality of the LSRs has led to their use as important tools in a number of genetic engineering applications in a wide variety of organisms. Given the important potential role of LSR enzymes in genetic engineering and gene therapy, understanding the structure and DNA-binding properties of LSRs is of fundamental importance for those seeking to enhance or alter specificity and functionality in these systems.
authors: Department of Biochemistry & Biophysics, Perelman School of Medicine, University of Pennsylvania , Philadelphia , USA.
authors: Gregory D
authors: GD
authors: Van Duyne
authors: Karen
authors: K
authors: Rutherford
mesh_terms: D000595:Amino Acid Sequence; D001287:Attachment Sites, Microbiological; D019426:Integrases / Q000378:metabolism; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D045522:Recombinases / Q000737:chemistry* / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*
chemical_list: D045522:Recombinases; D012694:Serine; D019426:Integrases