Biology Reference
In-Depth Information
F
IG
. 7. Organization of the Zn
2
þ
-binding site of
B. subtilis
MutL. (A) Detailed view of the
endonuclease site of
B. subtilis
MutL (PDB ID: 3KDK) with the conserved motifs shown in yellow
(DQHAX
2
EX
4
E), cyan (SCK), and green (CPHRGP). The side chains of the conserved residues
defining the metal-binding sites are shown as color-coded sticks and labeled. The zinc metal ions
occupying sites A and B are shown as purple spheres and labeled. The two structured water
molecules completing the tetrahedral coordination are omitted for clarity. (B) Detailed view of
the Zn
2
þ
-binding site of
S. gordonii
ScaR (PDB ID: 3HRU) shown on the same orientation and
color coding as in (A). Notice that in this case the metal ion is fully coordinated by protein side
chains, as opposed to MutL where the fourth ligand is provided by a water molecule. (C) Detailed
view of the primary (Pri) and ancillary (Anc) metal-binding sites of a two-domain variant of
M.
tuberculosis
IdeR (PDB ID: 2ISY) shown on the same orientation and color coding as in (A). The
Ni
2
þ
metal ions are shown as green spheres. The ancillary metal ion (Ni
2
þ
) is coordinated by the
side chains of His79, Glu83, and His98 and the octahedral coordination of this metal ion is
completed by one of the oxygens of a well-ordered phosphate group (shown as color-coded sticks)
and two water molecules (omitted for clarity). These water molecules are absent on the structure of
full-length IdeR,
119
where the side chains of Glu172 and Gln175 complete the coordination shell of
the ancillary metal ion-binding site. The Ni
2
þ
at the primary metal-binding site is coordinated by
the side chains of Met10, oxidized Cys102 (labeled hCys102), Glu105, and His106, as well as the
main chain of Cys102 and two water molecules (also omitted for clarity).
subdomains of the protein is highly variable, except when Zn
2
þ
is bound to
MutL. Upon metal binding, both protomers of the dimer adopt exactly the
same conformation,
96
suggesting that Zn
2
þ
binding restricts the flexibility
between the external and dimerization subdomains. Indeed, ''site A'' has a
coordination number characteristic of structural Zn
2
þ
metal ions—as opposed
to penta- or hexacoordination that is preferred for catalytic Zn
2
þ
metal
ions
128,129
—supporting the hypothesis that the metal bound to this site has a
structural role.
The Zn
2
þ
metal-binding site found in MutL closely resembles the second-
ary metal-binding site found in
Streptococcus gordonii
ScaR, a Mn
2
þ
-
dependent transcriptional regulator from the DtxR/MntR family (
Fig. 7
B).
130
Members of this family maintain manganese and iron homeostasis by down-
regulating metal uptake systems.
131-133
Direct binding of Mn
2
þ
or Fe
2
þ
—and
to a lesser extent other transition metal ions such as Ni
2
þ
,Zn
2
þ
,Co
2
þ
, and
