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Nucleic Acids Research Advance Access originally published online on March 16, 2007
Nucleic Acids Research 2007 35(7):2227-2237; doi:10.1093/nar/gkm045
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Nucleic Acids Research, 2007, Vol. 35, No. 7 2227-2237
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Nucleic Acid Enzymes

Topology of Type II REases revisited; structural classes and the common conserved core

Masha Y. Niv1,*, Daniel R. Ripoll2, Jorge A. Vila3, Adam Liwo3, Éva S. Vanamee4, Aneel K. Aggarwal4, Harel Weinstein1 and Harold A. Scheraga3

1Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA, 2Computational Biology Service Unit, Cornell Theory Center and 3Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA and 4Department of Molecular Physiology and Biophysics, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA

*To whom correspondence should be addressed. Tel: +1-212 746 6384; Fax: +1-212 746 8690; Email: man2016{at}med.cornell.edu

Received September 20, 2006. Revised January 10, 2007. Accepted January 11, 2007.

Type II restriction endonucleases (REases) are deoxyribonucleases that cleave DNA sequences with remarkable specificity. Type II REases are highly divergent in sequence as well as in topology, i.e. the connectivity of secondary structure elements. A widely held assumption is that a structural core of five ß-strands flanked by two {alpha}-helices is common to these enzymes. We introduce a systematic procedure to enumerate secondary structure elements in an unambiguous and reproducible way, and use it to analyze the currently available X-ray structures of Type II REases. Based on this analysis, we propose an alternative definition of the core, which we term the {alpha}ß{alpha}-core. The {alpha}ß{alpha}-core includes the most frequently observed secondary structure elements and is not a sandwich, as it consists of a five-strand ß-sheet and two {alpha}-helices on the same face of the ß-sheet. We use the {alpha}ß{alpha}-core connectivity as a basis for grouping the Type II REases into distinct structural classes. In these new structural classes, the connectivity correlates with the angles between the secondary structure elements and with the cleavage patterns of the REases. We show that there exists a substructure of the {alpha}ß{alpha}-core, namely a common conserved core, ccc, defined here as one {alpha}-helix and four ß-strands common to all Type II REase of known structure.


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