Abstract
I-TevI, a member of the GIY-YIG family of homing endonucleases, consists of an N-terminal catalytic domain and a C-terminal DNA-binding domain joined by a flexible linker. The GIY-YIG motif is in the N-terminal domain of I-TevI, which corresponds to a phylogenetically widespread catalytic cartridge that is often associated with mobile genetic elements. The crystal structure of the catalytic domain of I-TevI, the first of any GIY-YIG endonuclease, reveals a novel α/β-fold with a central three-stranded antiparallel β-sheet flanked by three helices. The most conserved and putative catalytic residues are located on a shallow, concave surface and include a metal coordination site. Similarities in the three-dimensional arrangement of the catalytically important residues and the cation-binding site with those of the His-Cys box endonuclease I-PpoI suggest the possibility of mechanistic relationships among these different families of homing endonucleases despite completely different folds.
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Acknowledgements
We thank J. Bujnicki for providing the coordinates of the computational model of the I-TevI N-terminal domain and A. Dean and D. Edgell for critically reading the manuscript. We thank B. Stoddard for insightful comments on an earlier version of this paper. This research is supported by grants from the National Institutes of Health to P.V.R. and M.B. The X-ray diffraction facilities at beamline X12C of the NSLS are supported by the DOE and by grants from the NIH.
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Van Roey, P., Meehan, L., Kowalski, J. et al. Catalytic domain structure and hypothesis for function of GIY-YIG intron endonuclease I-TevI. Nat Struct Mol Biol 9, 806–811 (2002). https://doi.org/10.1038/nsb853
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DOI: https://doi.org/10.1038/nsb853
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