The bacterial enzyme KsgA catalyzes the transfer of a total of four methyl groups from S-adenosyl-l-methionine (S-AdoMet) to two adjacent adenosine bases in 16S rRNA. This enzyme and the resulting modified adenosine bases appear to be conserved in all species of eubacteria, eukaryotes, and archaebacteria, and in eukaryotic organelles. Bacterial resistance to the aminoglycoside antibiotic kasugamycin involves inactivation of KsgA and resulting loss of the dimethylations, with modest consequences to the overall fitness of the organism. In contrast, the yeast ortholog, Dim1, is essential. In yeast, and presumably in other eukaryotes, the enzyme performs a vital role in pre-rRNA processing in addition to its methylating activity. Another ortholog has been discovered recently, h-mtTFB in human mitochondria, which has a second function; this enzyme is a nuclear-encoded mitochondrial transcription factor. The KsgA enzymes are homologous to another family of RNA methyltransferases, the Erm enzymes, which methylate a single adenosine base in 23S rRNA and confer resistance to the MLS-B group of antibiotics. Despite their sequence similarity, the two enzyme families have strikingly different levels of regulation that remain to be elucidated. We have crystallized KsgA from Escherichia coli and solved its structure to a resolution of 2.1A. The structure bears a strong similarity to the crystal structure of ErmC' from Bacillus stearothermophilus and a lesser similarity to sc-mtTFB, the Saccharomyces cerevisiae version of h-mtTFB. Comparison of the three crystal structures and further study of the KsgA protein will provide insight into this interesting group of enzymes.
RsmA (formerly KsgA) dimethylates two very conserved adjacent adenosines (positions 1518 and 1519) in the loop of a conserved hairpin h45 near the 3′-end of 16S rRNA. RsmA recognizes its substrate adenosine residues only in the context of a near mature 30S subunit and is required for the efficient processing of the rRNA termini during ribosome biogenesis dual function). AdoMet is the methyl group donor. RsmA (Dim1p) is the yeast ortholog. They belong to the erm family of methyltransferase responsible for erythromycin resistance. Notice, the acronym RsmA has also been used for for Regulator of Secondary Metabolism A, a protein not related to the RNA small subunit Methyltransferase. Structure of the E. coli methyltransferase RsmA bound to the E. coli 30S ribosomal subunit was solved (4ADV).
M
N
N
R
V
H
Q
G
H
L
A
R
K
R
F
G
Q
N
F
L
N
D
Q
F
V
I
D
S
I
V
S
A
I
N
P
Q
K
G
Q
A
M
V
E
I
G
P
G
L
A
A
L
T
E
P
V
G
E
R
L
D
Q
L
T
V
I
E
L
D
R
D
L
A
A
R
L
Q
T
H
P
F
L
G
P
K
L
T
I
Y
Q
Q
D
A
M
T
F
N
F
G
E
L
A
E
K
M
G
Q
P
L
R
V
F
G
N
L
P
Y
N
I
S
T
P
L
M
F
H
L
F
S
Y
T
D
A
I
A
D
M
H
F
M
L
Q
K
E
V
V
N
R
L
V
A
G
P
N
S
K
A
Y
G
R
L
S
V
M
A
Q
Y
Y
C
N
V
I
P
V
L
E
V
P
P
S
A
F
T
P
P
P
K
V
D
S
A
V
V
R
L
V
P
H
A
T
M
P
H
P
V
K
D
V
R
V
L
S
R
I
T
T
E
A
F
N
Q
R
R
K
T
I
R
N
S
L
G
N
L
F
S
V
E
V
L
T
G
M
G
I
D
P
A
M
R
A
E
N
I
S
V
A
Q
Y
C
Q
M
A
N
Y
L
A
E
N
A
P
L
Q
E
S