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