Nucleic Acids Research, 2000, Vol. 28, No. 5 1259-1265
© 2000 Oxford University Press
Intermolecular interactions and water structure in a condensed phase B-DNA crystal
Chemistry Department, University of Auckland, Auckland, New Zealand, 1Trescowthick Research Laboratories, Peter MacCallum Cancer Research Institute, Melbourne, Australia and 2Chemistry Department, University of Melbourne, Melbourne, Australia
By controlled dehydration, the unit cells of dodecamer DNA–drug crystals have been shrunk from 68 000 (normal state) to 60 000 (partially dehydrated intermediate state) to 51 000 Å3 (fully dehydrated state), beyond which no further solvent loss occurs. The total solvent content in the normal crystals is ~40% by volume, reducing to ~20% in the fully dehydrated phase. The 25% reduction in cell volume induced a dramatic enhancement in the resolution of the X-ray diffraction data (from 2.6 to beyond 1.5 Å). We have determined the structures of the normal, partially dehydrated and fully dehydrated crystals. Details of the ligand binding have been presented in the preceding article. The present paper describes the unique features of the structure of the fully dehydrated phase. This structure was refined with 9015 unique observed reflections to R = 14.9%, making it one of the most reliable models of B-form DNA available. The crystals exist as infinite polymeric networks, in which neighbouring dodecamer duplexes are crosslinked through phosphate oxygens via direct bonding to magnesium cations. The DNA is packed so tightly that there is essentially only a single layer of solvent between adjacent molecules. The details of the crystal packing, magnesium bridging, DNA hydration and DNA conformation are described and compared with other experimental evidence related to DNA condensation.
* To whom correspondence should be addressed. Tel: +64 9 373 7599; Fax: +64 9 373 7422; Email: g.clark@auckland.ac.nz Present addresses: Christopher J. Squire, Center for Advanced Biotechnology and Medicine and Rutgers University, 679 Hoes Lane, Piscataway, NJ 08854, USA L. J. Baker, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors