Biology Reference
In-Depth Information
Analysis of mercuric acetate-soaked crystals suggests the presence of
four putative Zn
2+
-binding sites per dimer. It has been proposed that one
of them is formed by a molecule of water and residues from each mono-
mer near the α3 helices: Cys
61
, Asp
64
and His
97
. The other Zn
2+
-binding
site might involve residues Asp
104
and His
106
from one monomer and
His
117
and Glu
120
from the other monomer, bridging α5 helices (
Cook
et al., 1998
). The proposed DNA recognition α-helix (αR) is highly con-
served among the SmtB/ArsR family members and it confers a high
degree of sequence identity (25-50%), allowing the generation of models
of SmtB/ArsR repressors based on the
Synechococcus
SmtB crystal structure
(
Busenlehner, Pennella, & Giedroc, 2003
).
Two characteristic metal-binding sites have been described in SmtB/
ArsR family members, the α3N and the α5 sites. It has been proposed that
the α3N-binding site senses larger, thiophilic metals such as Cd(II) or Pb(II)
and contains the highly conserved ELCVCDL sequence named the “metal
binding box”, whose cysteine pair may be important for metal recognition
(
Shi, Wu, & Rosen, 1994
). This metal-binding site is not regulatory in SmtB
(
VanZile, Chen, & Giedroc, 2002b
). However, substitution of both cysteine
residues in
Synechocystis
ZiaR inhibited metal responses in vivo (
Thelwell
et al., 1998
). Consistent with this, the second cysteine residue, Cys
74
, has
been suggested to be a critical metal ligand in
Anabaena
AztR (
Liu et al.,
2005
). In
Synechocystis
ArsR, its “metal binding box” EQCVCDL sequence
also contains the pair of cysteine residues suggested to interact with arse-
nite. To our knowledge, no studies about putative metal-binding sites in
Figure 4.4
Ribbon diagram of the crystal structure of the apo-SmtB dimer. The struc-
ture was imported from UniProt KB (access No 1SMT) and drawn with PyMol program
(ExPASy server). Each monomer shows an
ααααββα
fold (
Cook et al., 1998
). The
α
5,
α
3N
and
α
R helices are labelled. Residues from 1 to 24 have been added manually in the
figure. For colour version of this figure, the reader is referred to the online version of
this topic.
