 |
PDBsum entry 1prw
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Metal binding protein
|
PDB id
|
|
|
|
1prw
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
A closed compact structure of native ca(2+)-Calmodulin.
|
|
|
Authors
|
|
J.L.Fallon,
F.A.Quiocho.
|
|
|
Ref.
|
|
Structure, 2003,
11,
1303-1307.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Calmodulin has been a subject of intense scrutiny since its discovery because of
its unusual properties in regulating the functions of about 100 diverse target
enzymes and structural proteins. The original and to date only crystal
conformation of native eukaryotic Ca(2+)-calmodulin (Ca(2+)-CaM) is a very
extended molecule with two widely separated globular domains linked by an
exposed long helix. Here we report the 1.7 A X-ray structure of a new native
Ca(2+)-CaM that is in a compact ellipsoidal conformation and shows a sharp bend
in the linker helix and a more contracted N-terminal domain. This conformation
may offer advantages for recognition of kinase-type calmodulin targets or small
organic molecule drugs.
|
|
|
|
|
|
Figure 1.
Figure 1. Unbound Compact Structure of Native Ca^2+-CaM(A)
Stereoview of the electron density (2Fo-Fc at 1 s level) for the
N-domain of Ca^2+-CaM, showing the N-terminal acetoalanine
(n-ACE) and residues 2, 3, and 4 as a ball and stick model.
Carbon atoms are green, oxygens are red, and nitrogens are
blue.(B) Stereoview of the ribbon diagram of Ca^2+-CaM showing
interdomain contacts. The CaM backbone is purple, loops are
brown, and calciums are blue spheres. The sidechains that make
contact (including 16 hydrogen bonds (<3.4 Å) and 24 van der
Waals interactions (<4 Å)) between domains are shown (atom
colors as Figure 1A, with sulfur yellow). Helices are numbered
from I-VIII.
|
|
|
|
|
|
The above figure is
reprinted
by permission from Cell Press:
Structure
(2003,
11,
1303-1307)
copyright 2003.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Man bites dog.
|
|
|
Authors
|
|
W.E.Meador,
F.A.Quiocho.
|
|
|
Ref.
|
|
Nat Struct Biol, 2002,
9,
156-158.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Figure 1.
Figure 1. X-ray structures of the edema factor (EF) toxin. a,
Free EF and b, EF complexed with CaM and 3'deoxy-ATP. The EF
helical domain (yellow) is moved by the binding of calmodulin
(red), and held between it and the catalytic domains C[A] and
C[B] (green). Large conformational changes occur in the
interface domains switch A (blue), switch B (orange) and switch
C (cyan), which complete an active site in which 3' deoxy-ATP
and a metal are bound (purple). Figure courtesy of A. Bohm.
|
|
Figure 2.
Figure 2. Comparison of CaM -EF with other calmodulin structures
aligned on a CaM C-domain helix. a, Ca^2+ -calmodulin, with
the N-domain (orange) connected to the C-domain (red) by a rigid
linker helix. b, Ca^2+ -CaM enclosing a target domain (blue)
from myosin light chain kinase and c, a fragment of the
Ca^2+-activated K+ channel. Note that part of the linker helix
of CaM has become unwound to allow close binding of these quite
different targets. d, The CaM -EF structure. Calmodulin is held
between EF domains, again with a partially unwound linker, which
allows this unusual domain positioning. Also, note that the CaM
-EF structure does not have Ca^2+ in the CaM N-domain and the
CaM -K+ channel structure does not have Ca^2+ in the CaM
C-domain. Figure courtesy of W. Tang.
|
|
|
|
|
|
The above figures are
reproduced from the cited reference
with permission from Macmillan Publishers Ltd
|
|
|
Secondary reference #2
|
|
|
Title
|
|
X-Ray analysis reveals conformational adaptation of the linker in functional calmodulin mutants.
|
|
|
Authors
|
|
W.E.Meador,
S.E.George,
A.R.Means,
F.A.Quiocho.
|
|
|
Ref.
|
|
Nat Struct Biol, 1995,
2,
943-945.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #3
|
|
|
Title
|
|
Modulation of calmodulin plasticity in molecular recognition on the basis of X-Ray structures.
|
|
|
Authors
|
|
W.E.Meador,
A.R.Means,
F.A.Quiocho.
|
|
|
Ref.
|
|
Science, 1993,
262,
1718-1721.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #4
|
|
|
Title
|
|
Target enzyme recognition by calmodulin: 2.4 a structure of a calmodulin-Peptide complex.
|
|
|
Authors
|
|
W.E.Meador,
A.R.Means,
F.A.Quiocho.
|
|
|
Ref.
|
|
Science, 1992,
257,
1251-1255.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #5
|
|
|
Title
|
|
Calmodulin structure refined at 1.7 a resolution.
|
|
|
Authors
|
|
R.Chattopadhyaya,
W.E.Meador,
A.R.Means,
F.A.Quiocho.
|
|
|
Ref.
|
|
J Mol Biol, 1992,
228,
1177-1192.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Figure 2.
Figure 2. The K-termnal domain is shown including all sidechains and most of the water molecules (circle) in the
region i stereo. Polar side-chain interacting with water molecules are labeled. (Ball and stick.) Part of the cent~ral
a-helix can be seen close to the viewer, going left an down towards th c-domain, which is not shown in this ig.
Residues 8 to 72 are displayed in this Fig. The view is clse to that in Fig. 1, but not identicl. Calcium ions 1 and 2 ar
shown as triple concentric circles.
|
|
Figure 3.
Figure 3. The central cl-helix is shown in stereo, and ts polar residues labeled. (Ball and stick.) The view is diRerent
from Figs 2 and 4. The view is chosen so that the helix is seen vertical in this Fig. Some of the main-chain-side-chain and
side-chain-side-chain bonds can also be seen for residues belonging to this helix (described in able 4, sections D and E).
|
|
|
|
|
|
The above figures are
reproduced from the cited reference
with permission from Elsevier
|
|
|
|
|
|
|
