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

Masha Y. Niv*, Daniel R. Ripoll, Jorge A. Vila, Adam Liwo, Éva S. Vanamee, Aneel K. Aggarwal, Harel Weinstein, Harold A. Scheraga

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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 β-strands flanked by two α-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 αβα-core. The αβα-core includes the most frequently observed secondary structure elements and is not a sandwich, as it consists of a five-strand β-sheet and two α-helices on the same face of the β-sheet. We use the αβα-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 αβα-core, namely a common conserved core, ccc, defined here as one α-helix and four β-strands common to all Type II REase of known structure.

Original languageAmerican English
Pages (from-to)2227-2237
Number of pages11
JournalNucleic Acids Research
Volume35
Issue number7
DOIs
StatePublished - Apr 2007
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dr Richard J. Roberts for helpful discussions. This research was supported in part by NIH-GM-14312 and NIH-TW-6335 grants to H.A.S., NIH-GM-44006 grant to A.K.A., a Cornell/Weill grant to H.A.S. and H.W. and with the resources of the Computational Biology Service Unit from Cornell University that is partially funded by Microsoft Corporation, and of the Institute for Computational Biomedicine at Weill Cornell Medical College. Funding to pay the Open Access publication charge was provided by a Cornell/Weill grant to H.A.S and H.W.

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