BIOINORGANIC CHEMISTRY A Short Course Second Edition

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

fying pro - chiral atoms will be important in the discussion of the group I intron
(Section 6.2.3 ) and the hammerhead (Section 6.2.4 ) ribozymes.

6.2.3 The Group I Intron Ribozyme

Some group I introns contain an active site that allows them to cut themselves
out from a precursor RNA. In this self - splicing process, two exons are ligated
and ejected while the remaining intron becomes an intact messenger RNA,
transfer RNA, or ribosomal RNA.^15 While most introns are excised by the
spliceosome, a large ribonuceloprotein complex, the introns we discuss here
catalyze their own excision without assistance from any protein cofactors.^22
Divalent metal ions play a role in both conformation and catalysis; for instance,
group I self - splicing intron ribozymes require suffi cient magnesium ion
(approximately 2 mM) to promote effi cient folding. An exogenous guanosine
nucleoside cofactor is also required for the self - splicing reaction. The introns
are complex three - dimensional structures whose folding patterns are not com-
pletely understood. Most RNA ribozyme base pairs follow the Watson – Crick
hydrogen bonding pattern; however, Hoogsteen base pairing, mismatched
base pairs, and base triples (three bases connected by hydrogen bonds in
several specifi c, well - known patterns) are found, often near active sites.
The intron group I ribozymes feature common secondary structure and
reaction pathways. Active sites capable of catalyzing consecutive phosphodi-
ester reactions produce properly spliced and circular RNAs. Ribozymes fold
into a globular conformation and have solvent - inaccessible cores as quantifi ed
by Fe(II) - EDTA - induced free - radical cleavage experiments.^23 The Tetrahy-
mena group I intron ribozyme catalyzes phosphoryl transfer between guano-
sine and a substrate RNA strand — the exon. This ribozyme also has been
proposed to use metal ions to assist in proper folding, to activate the nucleo-
phile, and to stabilize the transition state. 27a
As stated previously in the introductory section, T. R. Cech and co - workers
reported on the fi rst catalytic RNA or ribozyme, the self - splicing intron of the

Figure 6.2 Identifying pro - R p and pro - S p oxygen atoms in RNA polymers.

O

O O

C

H

C

H

HC

H

C

H

C

H

C

H

C

Metal Ion

P

pro-Rp oxygen

3'

5'

5'

4'

4' 3' 2'

1

2

3

1'

O behind C

H

H C

H

O

O O

CH

C

H

C H Metal Ion

H

pro-Sp oxygen

1

2

3

3'

5'

4'

5'

3' 2'

4' 1'

P

O behind