Nucleic acid-metal ion interactions

448 Pages·2009·6.93 MB·English

by  Nicholas V. Hud

Nucleic Acid–Metal Ion Interactions
RSC Biomolecular Sciences
Editorial Board:
ProfessorStephenNeidle(Chairman),TheSchoolofPharmacy,UniversityofLondon,UK
DrSimonFCampbellCBE,FRS
DrMariusClore,NationalInstitutesofHealth,USA
ProfessorDavidMJLilleyFRS,UniversityofDundee,UK
ThisSeriesisdevotedtocoverageofthe interfacebetweenthe chemicalandbiological sciences,
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Titles in the Series:
BiophysicalandStructuralAspectsofBioenergetics
EditedbyMa˚rtenWikstro¨m,UniversityofHelsinki,Finland
ComputationalandStructuralApproachestoDrugDiscovery:Ligand–ProteinInteractions
EditedbyRobertMStroudandJanetFiner-Moore,UniversityofCaliforniainSanFrancisco,San
Francisco,CA,USA
ExploitingChemicalDiversityforDrugDiscovery
EditedbyPaulA.Bartlett,DepartmentofChemistry,UniversityofCalifornia,Berkeley,USAand
MichaelEntzeroth,S*BioPteLtd,Singapore
Metabolomics,MetabonomicsandMetaboliteProfiling
EditedbyWilliamJ.Griffiths,UniversityofLondon,TheSchoolofPharmacy,UniversityofLondon,
London,UK
NucleicAcid–MetalIonInteractions
EditedbyNicholasV.Hud,SchoolofChemistryandBiochemistry,GeorgiaInstituteofTechnology,
Atlanta,GA,USA
Protein–CarbohydrateInteractionsinInfectiousDisease
EditedbyCaroleA.Bewley,NationalInstitutesofHealth,Bethesda,Maryland,USA
ProteinFolding,MisfoldingandAggregation:ClassicalThemesandNovelApproaches
EditedbyVictorMun˜oz,DepartmentofChemistryandBiochemistry,UniversityofMaryland,MD,
USA
Protein-NucleicAcidInteractions:StructuralBiology
Edited by Phoebe A. Rice, Department of Biochemistry & Molecular Biology, The University of
Chicago, Chicago IL, USA and Carl C. Correll, Dept of Biochemistry and Molecular Biology,
RosalindFranklinUniversity,NorthChicago,IL,USA
QuadruplexNucleicAcids
EditedbyStephenNeidle,TheSchoolofPharmacy,UniversityofLondon,London,UKandShankar
Balasubramanian,DepartmentofChemistry,UniversityofCambridge,Cambridge,UK
RibozymesandRNACatalysis
Edited by David MJ Lilley FRS, University of Dundee, Dundee, UK and Fritz Eckstein, Max-
Planck-InstitutforExperimentalMedicine,Goettingen,Germany
Sequence-specificDNABindingAgents
EditedbyMichaelWaring,DepartmentofPharmacology,UniversityofCambridge,Cambridge,UK
StructuralBiologyofMembraneProteins
Edited by Reinhard Grisshammer and Susan K. Buchanan, Laboratory of Molecular Biology,
NationalInstitutesofHealth,Bethesda,Maryland,USA
Structure-basedDrugDiscovery:AnOverview
EditedbyRoderickE.Hubbard,UniversityofYork,UKandVernalis(R&D)Ltd,Cambridge,UK
TherapeuticOligonucleotides
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Nucleic Acid–Metal Ion
Interactions
Edited by
Nicholas V. Hud
School of Chemistry and Biochemistry, Georgia Institute of Technology,
Atlanta, GA, USA
ISBN: 978-0-85404-195-4
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Preface
Natural biochemical processes are continuously being discovered that involve
RNA. Some of these processes, such as RNA interference, are now being
exploitedforbiotechnologyandmedicinalapplications.DNAhasalsoproven
in recent years to be more than a passive storehouse of information. For
example, non-B-form DNA structures formed by G-rich DNA have been
shown to participate in the regulation of gene expression, a discovery that
presents new possibilities for drug targets in the genome. The current quest to
understandhownucleicacidsfunctionatthemostfundamentallevelsrequires
that we have a detailed understanding of nucleic acid–metal ion interactions.
Due to thepolyanionic nature ofnucleic acids, DNA and RNA molecules are
alwaysassociatedwithcationsinlivingcellsandthesecationsareessentialfor
maintaining nucleic acid structure and function. The nature of these inter-
actions varies greatly, from monovalent alkali metal ions that are primarily
delocalized in a diffuse cloud around duplex DNA and RNA, to transition
metals that are directly coordinated to the nucleotide bases. During the past
decade, manyimportant insightsregardingnucleicacid–metal ioninteractions
have resulted from the application of spectroscopic techniques in the solution
stateandthedeterminationofX-raycrystalstructures.Thepresentvolumehas
been compiled to provide readers with an overview of these biophysical
investigations. Our goal in writing each chapter has been two-fold. We have
soughttoproduceabookthatcouldserveasareferencesourceforresearchers
in the field, and also a text with sufficient background to serve as an initial
starting point for students and researchers interested in entering the field or
simply learning about this exciting topic.
As Editor, I am indebted to my co-authors for their generous contributions
tothisbook.Wehaveworkedtogethertomakethechaptersascomplementary
as possible and to minimize overlap.
RSCBiomolecularSciences
NucleicAcid–MetalIonInteractions
EditedbyNicholasV.Hud
rRoyalSocietyofChemistry2009
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v

Contents
Chapter 1 Complexes of Nucleic Acids with Group I and II Cations
Chiaolong Hsiao, Emmanuel Tannenbaum,
Halena VanDeusen, Eli Hershkovitz, Ginger Perng,
Allen R. Tannenbaum and Loren Dean Williams
1.1 Introduction 1
1.1.1 Modern Treasure Troves of Structural
Information: Large RNAs 2
1.2 Nucleic Acid Folding 2
1.2.1 Cations 2
1.2.2 The RNA Folding Hierarchy 3
1.2.3 Alternative RNA Folding Hierarchies 4
1.3 Coordination Chemistry 4
1.3.1 Group I 4
1.3.2 Group II 7
1.4 Experimental Methods for Determination
of Cation Positions in X-ray Structures 24
1.4.1 Group I 24
1.4.2 Group II 25
1.5 The Two Binding-mode Formalism 25
1.5.1 Thermodynamic/Kinetic Definition 25
1.5.2 Structural Definition 26
1.5.3 Computational Definition 26
1.5.4 Breaking the Two Binding-mode Formalism 27
1.6 Reaction Coordinates for RNA Folding 27
1.6.1 The Utility of 3D Databases for Determining
Mechanism 27
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NucleicAcid–MetalIonInteractions
EditedbyNicholasV.Hud
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viii Contents
1.6.2 Mg21–RNA Complexes Report on Folding
Intermediates 28
Appendix 28
Acknowledgements 32
References 32
Chapter 2 Coordinative Bond Formation Between Metal Ions and
Nucleic Acid Bases
Bernhard Lippert
2.1 Introduction 39
2.1.1 Nucleic Acids and Metal Ions 39
2.1.2 Types of Interactions 40
2.1.3 Brief History 41
2.1.4 Scope 42
2.2 Nucleobases as Ligands 42
2.2.1 Location of Donor Sites in DNA
and RNAs 42
2.2.2 Acid–Base Equilibria of Nucleobases 43
2.2.3 ‘Conventional’MetalBindingSitesinNeutral
Nucleobases 44
2.2.4 Exocyclic Amino Groups: Not Used Unless
Deprotonated 45
2.2.5 Metal Coordination to Rare Nucleobase
Tautomers 46
2.2.6 Deprotonated Nucleobases 48
2.2.7 Organometallic Nucleobase Complexes 50
2.2.8 Chelates, Macrochelates and ‘Indirect’
Chelates 52
2.2.9 Coordination Behavior of Di- and
Multinuclear Metal Complexes 52
2.2.10 Protonated Purine Bases as Ligands 54
2.2.11 Other Modes 54
2.2.12 Metal Migration 54
2.2.13 Metals as Chameleons in Nucleic Acid
Coordination 54
2.2.14 Complex Stabilities 55
2.3 Consequences of Metal Coordination 57
2.3.1 Cross-link Formation in dsDNA 57
2.3.2 Multistranded Nucleic Acids 59
2.3.3 Subtle Effects of Metal
Coordination 62
2.3.4 Irreversible Alterations 66
2.4 Summary and Outlook 68
References 69
Contents ix
Chapter 3 Sequence-specific DNA–Metal Ion Interactions
Nicholas V. Hud and Aaron E. Engelhart
3.1 Introduction 75
3.2 A Brief Overview of Cation Binding
Modes to DNA 77
3.3 Defining A-tracts, G-tracts and Generic DNA 79
3.4 Divalent Cation Localization 79
3.4.1 Divalent Cations and the Major Groove 79
3.4.2 Divalent Cations and the Minor Groove 86
3.5 Monovalent Cation Localization 92
3.5.1 Monovalent Cations and the Major Groove 92
3.5.2 Monovalent Cations and the Minor Groove 96
3.6 Testing Cation Size Selection of the A-tract
Minor Groove Using a Large Monovalent Cation 103
3.7 Additional Experimental Evidence of
Sequence-specific Binding of Cations to DNA 104
3.7.1 Capillary Electrophoresis 104
3.7.2 Hydration Measurements 104
3.8 Sequence-specific Cation Localization and DNA
Fine Structure 106
3.9 Investigations of the Role of Cations in DNA
Fine Structure Using Non-natural Bases 110
3.10 Conclusions and Perspectives 112
Acknowledgements 112
References 112
Chapter 4 Metal Ion Interactions with G-Quadruplex Structures
Aaron E. Engelhart, Janez Plavec, O¨zgu¨l Persil
and Nicholas V. Hud
4.1 Introduction 118
4.2 A Brief Overview of G-quadruplex Structures
and Folding Topologies 121
4.3 X-ray Crystallographic Studies of Cation
Coordination by G-quadruplexes 123
4.3.1 X-ray Studies of Monovalent Cation
Coordination 123
4.3.2 X-ray Studies of Divalent Cation
Coordination 128
4.4 NMR Studies of Cation Coordination
by G-quadruplexes 130
4.4.1 Solution-state NMR Studies of Monovalent
Cation Coordination 130