chapter 29 nucleic acid structures - personal.tcu.edupersonal.tcu.edu/yryu/50133/nucleic acd...
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Chapter 29
Nucleic acid structures
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Structures of A-, B-, and Z-DNA
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Structures of A-, B-, and Z-DNA
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Structural features of A-, B-, and Z-DNA
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Conversion of B-DNA to Z-DNA
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RNA can form an A helix
X-ray structure of a 10-bp RNA-DNA hybrid helix
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Sterically allowed orientations of bases
In most double helical nucleic acids, all bases are in the anti-conformation
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Nucleotide sugar conformations
(A-RNA or RNA-11)B-DNA
A-DNA
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Supercoiled DNA
• Compact packaging DNA in cells• Unwinding occurs in DNA replication and RNA transcription
Relaxed circle Tightly supercoiled
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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
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Topologically equivalent = the same L
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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
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Type IA topoisomerase action
Strand-passage mechanism
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Covalent enzyme-DNA intermediate
No energy is needed to reseal the nick in the DNA
5’
3’
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Structure of topoisomerase IA
E. coli topoisomerase III
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Strand-passage mechanism
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Structure of topoisomerase IB
Human topoisomerase I
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Controlled rotation mechanism
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Topoisomerase II action
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Structure of topoisomerase II
Yeast topoisomerase II (topo II)
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Mechanism of type II topoisomerase
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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)
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Watson-Crick base pairs
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Non Watson-Crick base pairs
A-T Hoogsteen pairA-A pair Hypothetical T-C pair
G-U Wobble pair in RNA structures
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Nucleic acid structures are stabilized by base stacking and hydrophobic interactions