BIOINORGANIC CHEMISTRY A Short Course Second Edition

264 GROUP I AND II METALS IN BIOLOGICAL SYSTEMS: GROUP II

step; and (3) the dissociation of the ribozyme products. The cleavage step is
the same for all hammerhead enzymes, and its mechanism is illustrated in
Figure 6.9. The catalytic rate of hammerhead transesterifi cation is 10^6 - fold that
of the non - enzymatic process.
Data on the X - ray crystallographic structures discussed in Section 6.2.4 are
collected in Table 6.3.
McKay and co - workers determined the X - ray crystallographic structure of
a hammerhead RNA – DNA ribozyme complex at 2.6 - Å resolution in 1994,
deposited in the Protein Databank (PDB) as 1HMH.^14 The substrate DNA
strand ensured that the complex would remain in the ground state since the
DNA 2 ′ - deoxy position could not undergo the cyclization/cleavage reaction.

Figure 6.10 Secondary structure of the RNA 6 hammerhead ribozyme as found in
the X - ray crystallographic structures PDB: 1HMH, 1MME, 299D, 300D, 301D, 359D,
379D, and 488D. A modifi ed RNA6 was used for crystal structures PDB: 1NYI, and
1Q29.

noncanonical bases

single hydrogen bonds between bases and backbone riboses

single hydrogen bonds between these bases

aromatic stabilization interactions between C17 and uridine turn of catalytic pocket

C

A

U

U

U

C

UA

A

C

G C

G C

C G

G A

A

A

A

A

C

A

C

C

A

C

U

C

U

U

G

G

G

G

17

1.5

1.4

1.3

1.2

1.1

2.5

2.4

2.3

2.2

2.1

4

5

6 3 Stem I

Catalytic Pocket

G

G

G

G

11.4

11.3

11.2

12

13

14

11.1 G

15.1

15.3

15.4

15.2

10.4

10.3

10.2

10.1

9

8

7

16.2

16.4

16.3

Stem II

Augmented

Stem II

Helix

Stem III

scissile bond

16.1

5' 3'

3'

5'

Hammerhead construct RNA 6: 16 nt ribozyme, 25 nt substrate.

Used for Scott group crystal structures and

biochemical experiments by Hampel and Burke, references 33, 56

Conserved residues underlined and italicized.

Figure key

Enzyme residues in bold and larger font size.

Substrate residues in plain text and smaller font size.

Cleavage site nucleotide, C17, in a dashed box.

Scissle C17-A1.1 phosphate bond marked

with arrow.