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Nucleic Acid Structure Dr. Helen Berman September 16, 2002 •Components •Sugar •Base •Phosphate •5’ to 3’ direction •RNA ribose •DNA deoxyribose •Numbering Voet, Donald and Judith G. Biochemistry. John Wiley & Sons, 1990, p. 792. •Names •Numbering •Bonding character •Position of hydrogen •tautomers Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 18. Tautomeric structures •Keto vs inol •How do we know? •Different hydrogen bonding patterns Saenger, Wolfram. Principles of Nucleic Acid Structure. Springer-Verlag New York Inc., 1984, p. 113. •pK of nucleotides •Effects on bases N1 adenine-3.5 N3 cytosine-4.2 N7 of adenine 1.0 Saenger, Wolfram. Principles of Nucleic Acid Structure. Springer-Verlag New York Inc., 1984, p. 109. Geometry of Watson Crick base pairs A:T and G:C are similar Voet, Donald and Judith G. Biochemistry. John Wiley & Sons, 1990, p. 797. The diversity of hydrogen bonding geometries Effects of pH Saenger, Wolfram. Principles of Nucleic Acid Structure. Springer-Verlag New York Inc., 1984, p. 120. Hydrogen bonding of WC base pair Definition of Major and Minor groove Mechanisms of recognition Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 90. Base-base pair T-A-T C-G-C (C must be protonated) Found in triple helices Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 68. Amino acid base pair Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 165. Amino acid base pair Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 165. Amino acidbase pair Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 166. Amino acid base pair Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 166. Base morphology Propeller twist Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 21. buckle Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 21. Base pair twist Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 22. roll Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 22. Backbone conformation Voet, Donald and Judith G. Biochemistry. John Wiley & Sons, 1990, p. 807. Anti vs. syn Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 27. Change in sugar conformation affects the backbone Voet, Donald and Judith G. Biochemistry. John Wiley & Sons, 1990, p. 808. Ribose ring is never flat Voet, Donald and Judith G. Biochemistry. John Wiley & Sons, 1990, p. 808. C4’-C5’-g+ Voet, Donald and Judith G. Biochemistry. John Wiley & Sons, 1990, p. 809. Conformation wheel for nucleotides a-3 values b-3 values g-3 values d-two ranges •C3’endo •C2’ endo e-trans-gz-3 values Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 28. Common building blocks Small changes leading to big differences A DNA B DNA B-DNA Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 34. A DNA Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, p. 36. Ch a r ac ter ist ics of ma jo r for m s of do u b le str an de d DNA Ove ra ll Gr oo ve s Polymer characteristics Sym m e try Ha n d e d n e ss Con fo r ma tio n Stac kin g A sm o o th sh o rt, fa t, b a se s tilted 2 m ajo r dee p m in o r sh all ow B sm o o th lo ng , thin, b a se s p e rpe nd icu la r 2 m ajo r w ide , dee p m in o r n ar row , dee p 2 diad s in p la n e b e tw ee n p la n e r ig ht C3 ' e n d o lo w a nt i sin gle nu cle ot ide r e p ea t Ba se -B a se in ea ch stra nd 2 diad s in p la n e b e tw ee n p la n e r ig ht C2 ' e n d o h ig h a nt i sin gle nu cle ot ide r e p ea t Ba se -B a se in ea ch stra nd Z zig -z a g 1 "mi nor gro o ve" side lin ed by ph o sph a te s "ma jo r g ro o ve " a to ms face co nv e x side 1 diad b e tw ee n p la n e lef t C3 ', C2 ' sy n a nt i 2 nu cle o tide r e p ea t int e rstr a n d b a se -b a se int e rstr a n d b a se -su ga r