Jürgen Sühnel jsuehnel@imb-jena.de

1. 3D Structures of Biological Macromolecules Part 2 Nucleic Acid Structures Jürgen Sühnel jsuehnel@imb-jena.de Institute of Molecular Biotechnology, Jena Centre for Bioinformatics Jena / Germany Supplementary Material: http://www.imb-jena.de/www_bioc/3D/

2. Molecules of Life

3. Nucleic Acids DNA genomic information RNA messenger RNA, ribosomal RNA, transfer RNA, ribozymes, small RNAs, noncoding RNAs, RNAi (gene silencing), aptamers (alternatives to antibodies) PNA peptide nucleic acids mimic nucleic acids

4. New Roles for RNA

5. New Roles for RNA Couzin J. Breakthrough of the year. Small RNAs make big splash.Science.2002, 298, 2296-2297.

8. From Gene to Protein

9. History

10. History

11. Nucleic Acid Structure

13. Nucleobases

14. Chain Direction in Nucleic Acids /web.siumed.edu/~bbartholomew/course_material/nucleic_acids.html

15. Chain Direction in Nucleic Acids

16. Nucleic Acid Backbone

17. Nucleic Acid Backbone Torsion Angles

18. Ribonucleotides and Deoxyribonucleotides

19. Nucleic Acid Base Pairs The ten possible purine-pyrimidine base pairs. Source: Ignacio Tinoco, Jr. in Gesteland, R. F. and Atkins, J. F. (1993) THE RNA WORLD. Cold Spring Harbor Laboratory Press.

20. Nucleic Acid Base Pairs The seven possible homo-purine base pairs. Source: Ignacio Tinoco, Jr. in Gesteland, R. F. and Atkins, J. F. (1993) THE RNA WORLD. Cold Spring Harbor Laboratory Press.

21. Nucleic Acid Base Pairs The four possible hetereo-purine base pairs. Source: Ignacio Tinoco, Jr. in Gesteland, R. F. and Atkins, J. F. (1993) THE RNA WORLD. Cold Spring Harbor Laboratory Press.

22. Nucleic Acid Base Pairs The seven possible pyrimidine-pyrimidine base pairs.

23. DNA Hydration www.lsbu.ac.uk/water/nucleic.html

24. Nucleic Acid Base Pairs – Water-mediated Pairs

25. Nucleic Acid Base Pairs – Water-mediated Pairs

26. Nucleic Acid Base Pairs – Water-mediated Pairs

27. Nucleic Acid Base Pairs with C-H…O/N Interactions

28. Nucleic Acid Base Pairs with C-H…O/N Interactions

29. Non-Canonical Base Pair Database http://prion.bchs.uh.edu/bp_type/

30. Selected Base Triples

31. Base Triples in tRNA Base triads in the crystal structure of yeast phenylalanine transfer RNA (PDB code: 4tna).

32. Base Tetrads in a DNA Tetraplex Parallel-stranded DNA tetraplex formed from the Tetrahymena telomeric sequence d(TTGGGGT) solved by NMR spectroscopy (PDB code: 139d). The structure contains four stacked G-tetrads in the center and additional T-tetrads.

33. Base Polyads

34. Base Polyads Base triads and a heptad in the crystal structure of a pseudoknot from beet western yellow virus (BWYV) involved in frameshifting (PDB code: 437d). The heptad is formed from two triads linked by A25.

35. HBexplore – H-bond Analysis in Proteins and Nucleic Acids www.imb-jena.de/www_bioc/hbx/hbx.html

36. Geometrical Parameters for Base Pairs in Nucleic Acids ndbserver.rutgers.edu/archives/report/tsukuba_sup/bp_step_hel.html

37. Nucleic Acid Structure

38. Nucleic Acid Structure – Sugar Conformation

39. Nucleic Acid Structure – Sugar Conformation

40. Nucleic Acid Structure – Sugar Conformation

41. Nucleic Acid Structure P:         P is the pitch of the helix corresponding to the distance between a base and the base obtained after walking along the DNA one full turn of 360°. n:         n is the number on nucleotides within one pitch. h:         distance between base planes. online-media.uni-marburg.de/chemie/bioorganic/vorlesung1/kapitel1e.html?/chemie/bioorganic/vorlesung1/k1e-20.html

42. DNA Conformations A B Z www.rcsb.org/pdb/molecules/pdb23_3.html

43. Ideal DNA Conformations and a Real B-DNA Structure

44. Nucleic Acid Conformations • B-DNA is found at low salt concentrations. It is believed to be the native conformation occurring in chromatin. • In the cell nucleus DNA is complexed with about an equivalent mass of protein to form a structure • known as chromatin. Chromatin is a periodic structure made up of repeating, regularly spaced • subunits, the subunit being the nucleosome. Within the nucleosomes the major part of DNA is • wrapped around histones. The remaining DNA joining each nucleosome is known as linker DNA. • A-DNA In solutions with higher salt concentrations or with alcohol added A-DNA is found. • Z-DNA occurs for alternating poly(dG-dC) sequences in solutions with high salt concentrations or alcohol. • RNA occurs (contrary to DNA) almost exclusively in the A-conformation (or in a related A'-form). • There are further nucleic acid conformations like C-DNA, H-DNA or others which are not discussed • here. • Geometrical features: • The distance between two subsequent base pairs along the helical axis is called helical rise (h). • The pitch (p) is the length of the helix axis for one complete helix turn. • The turn angle per nucleotide or twist angle (t) is given by 360° / number of nucleotides per turn. • C2'-endo and C3'-endo are descriptions of sugar conformations. • The most frequently occurring nucleic acid model conformations are characterized by the following geometrical • parameters : • A-DNA • right-handed helix; sugar pucker: C3'-endo; number of nucleotides per pitch: 11; h: 2.56 Å; t: +32.7°. • B-DNA • right-handed helix; sugar pucker: C2'-endo; number of nucleotides per pitch: 10; h: 3.38 Å; t: +36° . • Z-DNA • left-handed helix; G: syn conformation; sugar pucker: C3'-endo; C: anti conformation, sugar pucker: C2' • endo; number of nucleotides per pitch: 6x2; h: 3.7x2 Å; t= -30°x2 (for Z-DNA the repeat unit is the dimer • (G-C)2.

45. Nucleic Acid Conformations

46. Nucleic Acid Conformations - B-DNA

47. Nucleic Acid Conformations - B-DNA

48. Nucleic Acid Conformations – B-DNA

49. Nucleic Acid Conformations – B-DNA

50. First Single-crystal DNA Structure (B-DNA) Drew-Dickerson structure H. R. Drew, R. M. Wing, T. Takano, C. Broka, S. Tanaka, K. Itakura, R. E. Dickerson Structure Of A B-/DNA Dodecamer. Conformation And Dynamics Proc. Nat. Acad. Sci. Usa V. 78 2179 1981