Chapter 29 Nucleic acid structures - personal.tcu.edupersonal.tcu.edu/yryu/50133/Nucleic acd...
Transcript of Chapter 29 Nucleic acid structures - personal.tcu.edupersonal.tcu.edu/yryu/50133/Nucleic acd...
Chapter 29
Nucleic acid structures
Structures of A-, B-, and Z-DNA
Structures of A-, B-, and Z-DNA
Structural features of A-, B-, and Z-DNA
Conversion of B-DNA to Z-DNA
RNA can form an A helix
X-ray structure of a 10-bp RNA-DNA hybrid helix
Sterically allowed orientations of bases
In most double helical nucleic acids, all bases are in the anti-conformation
Nucleotide sugar conformations
(A-RNA or RNA-11)B-DNA
A-DNA
Supercoiled DNA
• Compact packaging DNA in cells• Unwinding occurs in DNA replication and RNA transcription
Relaxed circle Tightly supercoiled
Superhelix topology
• Linking number (L)– The number of times the one strand of the duplex passes the
other– Constant integer while the duplex remains covalently intact
• Twist (T) – The number of complete revolutions that the one strand makes
around the duplex axis• Writhing number (W)
– The number of turns that the duplex axis makes around the superhelix axis
– The number of supercoils present – Right handed supercoil is negative and left handed is positive
L = T + W
Topologically equivalent = the same L
Topoisomerases
• Type I : Transient single-strand breaks in DNA, changing linking number by 1 – Type IA: Strand-passage mechanism with 5’-phosphotyrosine
enzyme-DNA intermediate e.g. E. coli topoisomerase III
– Type IB: Controlled rotation mechanism with 3’-phosphotyrosine enzyme-DNA intermediate
e.g. Human topoisomerase I• Type II : Transient double-strand breaks in DNA
with ATP hydrolysis, changing linking number by 2e.g. Bacterial DNA gyrase, yeast topoisomerase II
Control of topological state (linking number) of DNA
Type IA topoisomerase action
Strand-passage mechanism
Covalent enzyme-DNA intermediate
No energy is needed to reseal the nick in the DNA
5’
3’
Structure of topoisomerase IA
E. coli topoisomerase III
Strand-passage mechanism
Structure of topoisomerase IB
Human topoisomerase I
Controlled rotation mechanism
Topoisomerase II action
Structure of topoisomerase II
Yeast topoisomerase II (topo II)
Mechanism of type II topoisomerase
Inhibitors of topoisomearasesas antibiotics and anticancer agents
(Bacterical DNA gyrase inhibitor)
(Bacterical DNA gyrase inhibitor) (Eukaryotic type II topoisomerase inhibitor)
(Eukaryotic type II topoisomerase inhibitor)
(Type IB topoisomerase inhibitor)
Watson-Crick base pairs
Non Watson-Crick base pairs
A-T Hoogsteen pairA-A pair Hypothetical T-C pair
G-U Wobble pair in RNA structures
Nucleic acid structures are stabilized by base stacking and hydrophobic interactions