1H,15N and 13C assigned Chemical Shifts for a complex of calmodulin with a
peptide of the olfactory CNGC channel

PDB 1CFF
A Chain A,NMR solution structure of A complex of calmodulin with A Binding
Peptide Of The Ca2+-Pump.
PDB 1DMO
Calmodulin, NMR ,30 structures.
PDB 1CDL
B Chain B, calmodulin complexed with calmodulin-binding peptide F.
PDB 1CFC
Calcium-free calmodulin.
PDB 1CTR
Calcium complexed with Trifluoperazine (1:1).
PDB 1CLL
Calmodulin (vertebrate).
PDB 1LIN
Calmodulin complexed with Trifluoperazine (1:4).
PDB 1CM1
A Chain A,Motions of calmodulin-Single-conformer-refinement.
PDB 1CM4
A Chain A,Motions of calmodulin-Four-conformer-refinement.
PDB 1MUX
Solution NMR structureof calmodulinW-7 Complex:
the basis of diversity in molecular recognition, 30 structures.
PDB 1CKK
A chain A,calmodulinRAT Ca2+calmodulin dependent protein kinase fragment.
PDB 1A29
Calmodulin Complexed With Trifluoperazine (1:2 Complex).
PDB 1QIV
A Chain A, Calmodulin Complexed With N-(3,3,-Diphenylpropyl)-N'-
[1-R-( 3,4-Bis-Butoxyphenyl)-Ethyl]-Propylenediamine (Dpd), 1:2 Complex.
PDB 1QIW
A Chain A, Calmodulin Complexed With N-(3,3,-Diphenylpropyl)-N'-
[1-R-( 3,4-Bis-Butoxyphenyl)-Ethyl]-Propylenediamine (Dpd).

Calmodulin-olfactory channel peptide complex

A Chain A,NMR solution structure of A complex of calmodulin with A Binding Peptide Of The Ca2+-Pump

B Chain B, calmodulin complexed with calmodulin-binding peptide F.

Calcium complexed with Trifluoperazine (1:1)

Calmodulin complexed with Trifluoperazine (1:4)

A Chain A,Motions of calmodulin-Single-conformer-refinement

A Chain A,Motions of calmodulin-Four-conformer-refinement

Solution NMR structureof calmodulinW-7 Complex:
the basis of diversity in molecular recognition,30 structures

A chain A,calmodulinRAT Ca2+calmodulin dependent protein kinase fragment.

Calmodulin Complexed With Trifluoperazine (1:2 Complex)

\\A Chain A, Calmodulin Complexed With N-(3,3,-Diphenylpropyl)-N'-[1-R-( 3,4-Bis-Butoxyphenyl)-Ethyl]-Propylenediamine (Dpd), 1:2 Complex\\

\\A Chain A, Calmodulin Complexed With N-(3,3,-Diphenylpropyl)-N'-[1-R-( 3,4-Bis-Butoxyphenyl)-Ethyl]-Propylenediamine (Dpd)\\

Information obtained from PDB's Chemical Component Dictionary
at http://wwpdb-remediation.rutgers.edu/downloads.html
Downloaded on Thu Jul 21 10:35:28 2011

Two distinct calcium-calmodulin interactions with N-terminal regions of the olfactory and rod cyclic nucleotide-gated channels characterized by NMR spectroscopy.

The three-dimensional structure of the complex between calmodulin (CaM) and a
peptide corresponding to the N-terminal portion of the CaM-binding domain of
the plasma membrane calcium pump, the peptide C20W, has been solved by
heteronuclear three-dimensional nuclear magnetic resonance (NMR) spectroscopy.
The structure calculation is based on a total of 1808 intramolecular NOEs and
49 intermolecular NOEs between the peptide C20W and calmodulin from
heteronuclear-filtered NOESY spectra and a half-filtered experiment,
respectively. Chemical shift differences between free Ca(2+)-saturated CaM and
its complex with C20W as well as the structure calculation reveal that C20W
binds solely to the C-terminal half of CaM. In addition, comparison of the
methyl resonances of the nine assigned methionine residues of free
Ca(2+)-saturated CaM with those of the CaM/C20W complex revealed a significant
difference between the N-terminal and the C-terminal domain; i.e., resonances
in the N-terminal domain of the complex were much more similar to those
reported for free CaM in contrast to those in the C-terminal half which were
significantly different not only from the resonances of free CaM but also from
those reported for the CaM/M13 complex. As a consequence, the global structure
of the CaM/C20W complex is unusual, i.e., different from other peptide
calmodulin complexes, since we find no indication for a collapsed structure.
The fine modulation in the peptide protein interface shows a number of
differences to the CaM/M13 complex studied by Ikura et al. [Ikura, M., Clore,
G. M., Gronenborn, A. M., Zhu, G., Klee, C. B., and Bax, A. (1992) Science 256,
632-638]. The unusual binding mode to only the C-terminal half of CaM is in
agreement with the biochemical observation that the calcium pump can be
activated by the C-terminal half of CaM alone [Guerini, D., Krebs, J., and
Carafoli, E. (1984) J. Biol. Chem. 259, 15172-15177].

Elshorst B, Hennig M, Forsterling H, Diener A, Maurer M, Schulte P, Schwalbe H,
Griesinger C, Krebs J, Schmid H, Vorherr T, Carafoli E.
NMR solution structure of a complex of calmodulin with a binding peptide of the Ca2+ pump.
Biochemistry. 1999 Sep 21;38(38):12320-32.

NMR solution structure of a complex of calmodulin with a binding peptide of the Ca2+ pump.

The solution structure of Ca(2+)-free calmodulin has been determined by NMR
spectroscopy, and is compared to the previously reported structure of the
Ca(2+)-saturated form. The removal of Ca2+ causes the interhelical angles of
four EF-hand motifs to increase by 36 degrees-44 degrees. This leads to major
changes in surface properties, including the closure of the deep hydrophobic
cavity essential for target protein recognition. Concerted movements of helices
A and D with respect to B and C, and of helices E and H with respect to F and G
are likely responsible for the cooperative Ca(2+)-binding property observed
between two adjacent EF-hand sites in the amino- and carboxy-terminal domains.

Zhang M, Tanaka T, Ikura M.
Calcium-induced conformational transition revealed by the solution structure
of apo calmodulin.
Nat Struct Biol. 1995 Sep;2(9):758-67.

Calcium-induced conformational transition revealed by the solution structure of apo calmodulin.

The crystal structure of calcium-bound calmodulin (Ca(2+)-CaM) bound to a
peptide analog of the CaM-binding region of chicken smooth muscle myosin light
chain kinase has been determined and refined to a resolution of 2.4 angstroms
(A). The structure is compact and has the shape of an ellipsoid (axial ratio
approximately 2:1). The bound CaM forms a tunnel diagonal to its long axis that
engulfs the helical peptide, with the hydrophobic regions of CaM melded into a
single area that closely covers the hydrophobic side of the peptide. There is a
remarkably high pseudo-twofold symmetry between the closely associated domains.
The central helix of the native CaM is unwound and expanded into a bend between
residues 73 and 77. About 185 contacts (less than 4 A) are formed between CaM
and the peptide, with van der Waals contacts comprising approximately 80% of
this total.

Meador WE, Means AR, Quiocho FA.
Target enzyme recognition by calmodulin: 2.4 A structure of a calmodulin-peptide complex.
Science. 1992 Aug 28;257(5074):1251-5.

Target enzyme recognition by calmodulin: 2.4 A structure of a calmodulin-peptide complex.

The three-dimensional structure of calmodulin in the absence of Ca2+ has been
determined by three- and four-dimensional heteronuclear NMR experiments,
including ROE, isotope-filtering combined with reverse labelling, and
measurement of more than 700 three-bond J-couplings. In analogy with the
Ca(2+)-ligated state of this protein, it consists of two small globular domains
separated by a flexible linker, with no stable, direct contacts between the two
domains. In the absence of Ca2+, the four helices in each of the two globular
domains form a highly twisted bundle, capped by a short anti-parallel
beta-sheet. This arrangement is qualitatively similar to that observed in the
crystal structure of the Ca(2+)-free N-terminal domain of troponin C.

Kuboniwa H, Tjandra N, Grzesiek S, Ren H, Klee CB, Bax A.
Solution structure of calcium-free calmodulin.
Nat Struct Biol. 1995 Sep;2(9):768-76.

Solution structure of calcium-free calmodulin.

The crystal structure of calmodulin (CaM) bound to trifluoperazine (TFP) has
been determined and refined to a resolution of 2.45 A. Only one TFP is bound to
CaM, but that is sufficient to cause distortion of the central alpha-helix and
juxtaposition of the N- and C-terminal domains similar to that seen in
CaM-polypeptide complexes. The drug makes extensive contacts with residues in
the C-terminal domain of CaM but only a few contacts with one residue in the
N-terminal domain. The structure suggests that substrate binding to the
C-terminal domain is sufficient to cause the conformational changes in
calmodulin that lead to activation of its targets.

Cook WJ, Walter LJ, Walter MR.
Drug binding by calmodulin: crystal structure of a calmodulin-trifluoperazine complex.
Biochemistry. 1994 Dec 27;33(51):15259-65.

Drug binding by calmodulin: crystal structure of a calmodulin-trifluoperazine complex.

We have determined and refined the crystal structure of a recombinant calmodulin
at 1.7 A resolution. The structure was determined by molecular replacement,
using the 2.2 A published native bovine brain structure as the starting model.
The final crystallographic R-factor, using 14,469 reflections in the 10.0 to
1.7 A range with structure factors exceeding 0.5 sigma, is 0.216. Bond lengths
and bond angle distances have root-mean-square deviations from ideal values of
0.009 A and 0.032 A, respectively. The final model consists of 1279
non-hydrogen atoms, including four calcium ions, 1130 protein atoms, including
three Asp118 side-chain atoms in double conformation, 139 water molecules and
one ethanol molecule. The electron densities for residues 1 to 4 and 148 of
calmodulin are poorly defined, and not included in our model, except for
main-chain atoms of residue 4. The calmodulin structure from our crystals is
very similar to the earlier 2.2 A structure described by Babu and coworkers
with a root-mean-square deviation of 0.36 A. Calmodulin remains a
dumb-bell-shaped molecule, with similar lobes and connected by a central
alpha-helix. Each lobe contains three alpha-helices and two Ca2+ binding EF
hand loops, with a short antiparallel beta-sheet between adjacent EF hand loops
and one non-EF hand loop. There are some differences in the structure of the
central helix. The crystal packing is extensively studied, and facile crystal
growth along the z-axis of the triclinic crystals is explained. Herein, we
describe hydrogen bonding in the various secondary structure elements and
hydration of calmodulin.

Chattopadhyaya R, Meador WE, Means AR, Quiocho FA.
Calmodulin structure refined at 1.7 A resolution.
J Mol Biol. 1992 Dec 20;228(4):1177-92.

Calmodulin structure refined at 1.7 A resolution.

Here we show that, as a consequence of binding the drug trifluoperazine, a major
conformational movement occurs in Ca(2+)-calmodulin (CaM). The tertiary
structure changes from an elongated dumb-bell, with exposed hydrophobic
surfaces, to a compact globular form which can no longer interact with its
target enzymes. It is likely that inactivation of Ca(2+)-CaM by trifluoperazine
is due to this major tertiary-structural alteration in Ca(2+)-CaM, which is
initiated and stabilized by drug binding. This conformational change is similar
to that which occurs on the binding of Ca(2+)-CaM to target peptides. Two
hydrophobic binding pockets, created by amino acid residues adjacent to
Ca(2+)-coordinating residues, form the key recognition sites on Ca(2+)-CaM for
both inhibitors and target enzymes.

Vandonselaar M, Hickie RA, Quail JW, Delbaere LT.
Trifluoperazine-induced conformational change in Ca(2+)-calmodulin.
Nat Struct Biol. 1994 Nov;1(11):795-801.

Trifluoperazine-induced conformational change in Ca(2+)-calmodulin.

BACKGROUND: Calmodulin is a calcium-activated regulatory protein which can bind
to many different targets. The protein resembles a highly flexible dumbbell,
and bends in the middle as it binds. This and other motions must be understood
to formulate a realistic model of calmodulin function. RESULTS: Using the Bragg
reflections from X-ray crystallography, a multiple-conformer refinement of a
calmodulin-peptide complex shows anisotropic displacements, with high
variations of dihedral angles in several nonhelical domains: the flexible
linker; three of the four calcium-binding sites (including both of the
N-terminal sites); and a turn connecting the C-terminal EF-hand calcium-binding
domains. Three-dimensional maps of the large scale diffuse X-ray scattering
data show isotropic liquid-like motions with an unusually small correlation
length. Three-dimensional maps of the small scale diffuse streaks show highly
coupled, anisotropic motions along the head-to-tail molecular packing direction
in the unit cell. There is also weak coupling perpendicular to the head-to-tail
packing direction, particularly across a cavity occupied by the disordered
linker domain of the molecule. CONCLUSIONS: Together, the Bragg and diffuse
scattering present a self-consistent description of the motions in the flexible
linker of calmodulin. The other mobile regions of the protein are also of great
interest. In particular, the high variations in the calcium-binding sites are
likely to influence how strongly they bind ions. This is especially important
in the N-terminal sites, which regulate the activity of the molecule.

Wall ME, Clarage JB, Phillips GN.
Motions of calmodulin characterized using both Bragg and diffuse X-ray scattering.
Structure. 1997 Dec 15;5(12):1599-612.

Motions of calmodulin characterized using both Bragg and diffuse X-ray scattering.

The solution structure of calcium-bound calmodulin (CaM) complexed with an
antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), has been
determined by multidimensional NMR spectroscopy. The structure consists of one
molecule of W-7 binding to each of the two domains of CaM. In each domain, the
W-7 chloronaphthalene ring interacts with four methionine methyl groups and
other aliphatic or aromatic side-chains in a deep hydrophobic pocket, the site
responsible for CaM binding to CaM-dependent enzymes such as myosin light chain
kinases (MLCKs) and CaM kinase II. This competitive binding at the same site
between W-7 and CaM-dependent enzymes suggests the mechanism by which W-7
inhibits CaM to activate the enzymes. The orientation of the W-7 naphthalene
ring in the N-terminal pocket is rotated approximately 40 degrees with respect
to that in the C-terminal pocket. The W-7 ring orientation differs
significantly from the Trp800 indole ring of smooth muscle MLCK bound to the
C-terminal pocket and the phenothiazine ring of trifluoperazine bound to the N
or C-terminal pocket. These comparative structural analyses demonstrate that
the two hydrophobic pockets of CaM can accommodate a variety of bulky aromatic
rings, which provides a plausible structural basis for the diversity in
CaM-mediated molecular recognition.

Osawa M, Swindells MB, Tanikawa J, Tanaka T, Mase T, Furuya T, Ikura M.
Solution structure of calmodulin-W-7 complex: the basis of diversity
in molecular recognition.
J Mol Biol. 1998 Feb 13;276(1):165-76.

Solution structure of calmodulin-W-7 complex: the basis of diversity in molecular recognition.

The structure of calcium-bound calmodulin (Ca2+/CaM) complexed with a 26-residue
peptide, corresponding to the CaM-binding domain of rat Ca2+/CaM-dependent
protein kinase kinase (CaMKK), has been determined by NMR spectroscopy. In this
complex, the CaMKK peptide forms a fold comprising an alpha-helix and a
hairpin-like loop whose C-terminus folds back on itself. The binding
orientation of this CaMKK peptide by the two CaM domains is opposite to that
observed in all other CaM-target complexes determined so far. The N- and
C-terminal hydrophobic pockets of Ca2+/CaM anchor Trp 444 and Phe 459 of the
CaMKK peptide, respectively. This 14-residue separation between two key
hydrophobic groups is also unique among previously determined CaM complexes.
The present structure represents a new and distinct class of Ca2+/CaM target
recognition that may be shared by other Ca2+/CaM-stimulated proteins.

Osawa M, Tokumitsu H, Swindells MB, Kurihara H, Orita M, Shibanuma T, Furuya T, Ikura M.
A novel target recognition revealed by calmodulin in complex with
Ca2+-calmodulin-dependent kinase kinase.
Nat Struct Biol. 1999 Sep;6(9):819-24.

A novel target recognition revealed by calmodulin in complex with Ca2+-calmodulin-dependent kinase kinase.

The NMRPipe system is a UNIX software environment of processing, graphics, and
analysis tools designed to meet current routine and research-oriented
multidimensional processing requirements, and to anticipate and accommodate
future demands and developments. The system is based on UNIX pipes, which allow
programs running simultaneously to exchange streams of data under user control.
In an NMRPipe processing scheme, a stream of spectral data flows through a
pipeline of processing programs, each of which performs one component of the
overall scheme, such as Fourier transformation or linear prediction. Complete
multidimensional processing schemes are constructed as simple UNIX shell
scripts. The processing modules themselves maintain and exploit accurate
records of data sizes, detection modes, and calibration information in all
dimensions, so that schemes can be constructed without the need to explicitly
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speeds, choice of both all-in-memory and disk-bound processing, easy adaptation
to different data formats, simpler software development and maintenance, and
the ability to distribute processing tasks on multi-CPU computers and computer
networks.

Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfeifer J, Bax A.
NMRPipe: a multidimensional spectral processing system based on UNIX pipes.
J Biomol NMR. 1995 Nov;6(3):277-93.

NMRPipe: a multidimensional spectral processing system based on UNIX pipes.

Johnson, B. and Blevins R.A.(1994)
J.Biomol.NMR, 4, 603-614
A computer program for the visualisation and analysis of NMR data.

Structure Of Calmodulin Complexed With A Fragment Of The Olfactory Cng Channel

cyclic nucleotide-gated olfactory channel [Bos taurus]

PREDICTED: cyclic nucleotide-gated olfactory channel isoform X1 [Bos taurus]

PREDICTED: LOW QUALITY PROTEIN: cyclic nucleotide-gated olfactory channel [Bison bison bison]

RecName: Full=Cyclic nucleotide-gated olfactory channel; AltName: Full=Cyclic nucleotide-gated cation channel 2; AltName: Full=

TPA: cyclic nucleotide-gated olfactory channel [Bos taurus]

Cyclic nucleotide-gated olfactory channel (Cyclic nucleotide-gated cation channel 2) (CNG channel alpha-2) (CNG-2) (CNG2)

cyclic nucleotide gated channel alpha 2 [Bos taurus]

A multidimensional spectral processing system based on UNIX pipes.
Delaglio,F.,Grzesiek,S.,Vuister,G.W.,Zhu,G.,Pfeifer,J. and Bax,A.(1995)
J.Biomol. NMR,6,277-293.

A computer program for the visualisation and analysis of NMR data.
Johnson,B. and Blevins,R.A. (1994)
J.Biomol. NMR,4,603-614.