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Exploring Nucleic Acid Structures . Nucleic Acid Building Blocks: Nucleotides. Base. Sugar. Phosphate. Bases. Pyrimidines and purines Positions of hydrogens key to recognition. DNA vs. RNA. Bases Purines and Pyrimidines Bases in DNA (dA, dT, dG, dC) Bases in RNA (A, U, G, C) Sugars
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Nucleic Acid Building Blocks: Nucleotides Base Sugar Phosphate
Bases • Pyrimidines and purines • Positions of hydrogens key to recognition
DNA vs. RNA Bases Purines and Pyrimidines Bases in DNA (dA, dT, dG, dC) Bases in RNA (A, U, G, C) Sugars DNA has deoxy ribose sugar RNA has ribose sugar deoxy-ribose ribose
Tautomeric structures • Keto vs inol • Different hydrogen bonding patterns
pK of nucleotides • Affects hydrogen bonding possibilities N1 adenine-3.5 N3 cytosine-4.2 N7 of adenine 1.0
Watson Crick Base Pairs Geometry of A:T and G:C base pairs are isosteric
Hydrogen bonding if WC base pair • Definition of Major and Minor groove • Mechanisms of recognition
Basepair-base • C-G-C (C must be protonated) • T-A-T normal • Found in triple helices
Conformation wheel for nucleotides • -3 values • -3 values • -3 values • -two ranges • C3’ endo • C2’ endo • -trans,g- • -3 values
Common building blocksSmall changes leading to big differences
ds DNA types B-DNA A-DNA Z-DNA
References Saenger, Wolfram. Principles of Nucleic Acid Structure. Springer-Verlag New York Inc., 1984, pp. 109, 113. Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, pp. 18, 21-22, 34, 36, 68, 90, 165-166. Voet, Donald and Judith G. Biochemistry. John Wiley & Sons, 1990, pp. 792, 797, 807-809.
Defined sequence DNA CGCGAATTCGCG • High propeller in center • Narrow minor groove
Z DNA • Left handed • Very deep minor groove • Major groove on outside Voet, Donald and Judith G. Biochemistry. John Wiley & Sons, 1990, p. 802.
Mismatches • Local changes • Global structure same as parent
PNA Triple strand • DNA strand + Peptide nucleic acid sequence
Diversity of folds • Two different dimer folds • Also possible • Single strand • Four strands
References Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, pp. 33-36, 76-77, 83, 97. Voet, Donald and Judith G. Biochemistry. John Wiley & Sons, 1990, pp. 796, 799, 800, 802.