spacer
spacer

PDBsum entry 1mux
Go to PDB code: 
protein ligands metals links
Calcium-binding PDB id
1mux

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chain
148 a.a. *
Ligands
WW7 ×2
Metals
_CA ×4
* Residue conservation analysis
PDB id:
1mux
Name: Calcium-binding
Title: Solution nmr structure of calmodulin/w-7 complex: the basis of diversity in molecular recognition, 30 structures
Structure: Calmodulin. Chain: a. Engineered: yes
Source: Xenopus laevis. African clawed frog. Organism_taxid: 8355. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 30 models
Authors: M.Osawa,M.B.Swindells,J.Tanikawa,T.Tanaka,T.Mase,T.Furuya,M.Ikura
Key ref:
M.Osawa et al. (1998). Solution structure of calmodulin-W-7 complex: the basis of diversity in molecular recognition. J Mol Biol, 276, 165-176. PubMed id: 9514729 DOI: 10.1006/jmbi.1997.1524
Date:
06-Sep-97     Release date:   14-Oct-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0DP33  (CALM1_XENLA) -  Calmodulin-1 from Xenopus laevis
Seq:
Struc: 		149 a.a.
148 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1006/jmbi.1997.1524 J Mol Biol 276:165-176 (1998)
PubMed id: 9514729  
 
 
Solution structure of calmodulin-W-7 complex: the basis of diversity in molecular recognition.
M.Osawa, M.B.Swindells, J.Tanikawa, T.Tanaka, T.Mase, T.Furuya, M.Ikura.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Fifty per cent inhibitory concentrations (IC50) for Ca 2+ -CaM dependent activation of phosphodiester- ase by W-7 derivatives containing a different substituent atom at position 5: W-7(H), W-7(F), W-7, W-7(Br), and W-7(I) (Tanaka et al., 1982; MacNeil et al., 1988). IC50 is plotted against van der Waals radius and electronegativ- ity (inset) for halogen atoms and hydrogen. 		Figure 8.
Figure 8. a, 1 H chemical shift changes for Ca 2+ -CaM methyl groups binding to W-7. b, W-7 binding site in the N-terminal domain; and c, W-7 binding site in the C-terminal domain of Ca 2+ -CaM complexed with W-7 and Ca 2+ -CaM (Chattopadhyaya et al., 1992). The C a carbon atoms are superimposed. Hydrophobic side-chains of Ca 2+ - CaM/W-7 complex within 5 Å of W-7 are shown in magenta, and corresponding side-chains of Ca 2+ - CaM are shown as blue sticks. W-7 is shown as a space-filling model with chlorine in orange, sulfur in yellow, oxygen in red, nitrogen in blue, carbon in green, and hydrogen in white.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 276, 165-176) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21506119 A.Sivanandam, S.Murthy, K.Chinnakannu, V.U.Bai, S.H.Kim, E.R.Barrack, M.Menon, and G.P.Reddy (2011).
Calmodulin protects androgen receptor from calpain-mediated breakdown in prostate cancer cells.
  J Cell Physiol, 226, 1889-1896.  
20010694 F.Rodríguez-Castañeda, M.Maestre-Martínez, N.Coudevylle, K.Dimova, H.Junge, N.Lipstein, D.Lee, S.Becker, N.Brose, O.Jahn, T.Carlomagno, and C.Griesinger (2010).
Modular architecture of Munc13/calmodulin complexes: dual regulation by Ca2+ and possible function in short-term synaptic plasticity.
  EMBO J, 29, 680-691.
PDB code: 2kdu
20116385 M.Oleszczuk, I.M.Robertson, M.X.Li, and B.D.Sykes (2010).
Solution structure of the regulatory domain of human cardiac troponin C in complex with the switch region of cardiac troponin I and W7: the basis of W7 as an inhibitor of cardiac muscle contraction.
  J Mol Cell Cardiol, 48, 925-933.
PDB code: 2krd
20532887 T.Sakamoto, H.Kitaura, M.Minami, Y.Honda, T.Watanabe, A.Ueda, K.Suzuki, and T.Irie (2010).
Transcriptional effect of a calmodulin inhibitor, W-7, on the ligninolytic enzyme genes in Phanerochaete chrysosporium.
  Curr Genet, 56, 401-410.  
20860665 X.H.Zhang, M.W.Jin, H.Y.Sun, S.Zhang, and G.R.Li (2010).
The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide directly blocks human ether à-go-go-related gene potassium channels stably expressed in human embryonic kidney 293 cells.
  Br J Pharmacol, 161, 872-884.  
19419198 R.M.Hoffman, and B.D.Sykes (2009).
Structure of the inhibitor W7 bound to the regulatory domain of cardiac troponin C.
  Biochemistry, 48, 5541-5552.
PDB code: 2kfx
17848620 E.E.Gardiner, D.Karunakaran, J.F.Arthur, F.T.Mu, M.S.Powell, R.I.Baker, P.M.Hogarth, M.L.Kahn, R.K.Andrews, and M.C.Berndt (2008).
Dual ITAM-mediated proteolytic pathways for irreversible inactivation of platelet receptors: de-ITAM-izing FcgammaRIIa.
  Blood, 111, 165-174.  
18462678 J.Gsponer, J.Christodoulou, A.Cavalli, J.M.Bui, B.Richter, C.M.Dobson, and M.Vendruscolo (2008).
A coupled equilibrium shift mechanism in calmodulin-mediated signal transduction.
  Structure, 16, 736-746.
PDB codes: 2k0e 2k0f
18819009 S.J.Abraham, S.Hoheisel, and V.Gaponenko (2008).
Detection of protein-ligand interactions by NMR using reductive methylation of lysine residues.
  J Biomol NMR, 42, 143-148.  
17227773 P.Sengupta, M.J.Ruano, F.Tebar, U.Golebiewska, I.Zaitseva, C.Enrich, S.McLaughlin, and A.Villalobo (2007).
Membrane-permeable calmodulin inhibitors (e.g. W-7/W-13) bind to membranes, changing the electrostatic surface potential: dual effect of W-13 on epidermal growth factor receptor activation.
  J Biol Chem, 282, 8474-8486.  
16643366 H.R.Lu, E.Vlaminckx, A.Van de Water, and D.J.Gallacher (2006).
Calmodulin antagonist W-7 prevents sparfloxacin-induced early afterdepolarizations (EADs) in isolated rabbit purkinje fibers: importance of beat-to-beat instability of the repolarization.
  J Cardiovasc Electrophysiol, 17, 415-422.  
16877516 J.H.Streiff, T.W.Allen, E.Atanasova, N.Juranic, S.Macura, A.R.Penheiter, and K.A.Jones (2006).
Prediction of volatile anesthetic binding sites in proteins.
  Biophys J, 91, 3405-3414.  
16721661 K.Chen, J.Ruan, and L.A.Kurgan (2006).
Prediction of three dimensional structure of calmodulin.
  Protein J, 25, 57-70.  
16240315 L.Milanesi, C.A.Hunter, S.E.Sedelnikova, and J.P.Waltho (2006).
Amplification of bifunctional ligands for calmodulin from a dynamic combinatorial library.
  Chemistry, 12, 1081-1087.  
16493654 P.Radivojac, S.Vucetic, T.R.O'Connor, V.N.Uversky, Z.Obradovic, and A.K.Dunker (2006).
Calmodulin signaling: analysis and prediction of a disorder-dependent molecular recognition.
  Proteins, 63, 398-410.  
16710297 Y.B.Ammar, S.Takeda, T.Hisamitsu, H.Mori, and S.Wakabayashi (2006).
Crystal structure of CHP2 complexed with NHE1-cytosolic region and an implication for pH regulation.
  EMBO J, 25, 2315-2325.
PDB code: 2bec
15596444 I.Horváth, V.Harmat, A.Perczel, V.Pálfi, L.Nyitray, A.Nagy, E.Hlavanda, G.Náray-Szabó, and J.Ovádi (2005).
The structure of the complex of calmodulin with KAR-2: a novel mode of binding explains the unique pharmacology of the drug.
  J Biol Chem, 280, 8266-8274.
PDB code: 1xa5
16368012 S.Abel, T.Savchenko, and M.Levy (2005).
Genome-wide comparative analysis of the IQD gene families in Arabidopsis thaliana and Oryza sativa.
  BMC Evol Biol, 5, 72.  
  15955874 S.McLaughlin, S.O.Smith, M.J.Hayman, and D.Murray (2005).
An electrostatic engine model for autoinhibition and activation of the epidermal growth factor receptor (EGFR/ErbB) family.
  J Gen Physiol, 126, 41-53.  
15498938 A.G.Turjanski, D.A.Estrin, R.E.Rosenstein, J.E.McCormick, S.R.Martin, A.Pastore, R.R.Biekofsky, and V.Martorana (2004).
NMR and molecular dynamics studies of the interaction of melatonin with calmodulin.
  Protein Sci, 13, 2925-2938.  
14695278 B.B.Adhikari, and K.Wang (2004).
Interplay of troponin- and Myosin-based pathways of calcium activation in skeletal and cardiac muscle: the use of W7 as an inhibitor of thin filament activation.
  Biophys J, 86, 359-370.  
15489172 J.S.Shim, J.Lee, H.J.Park, S.J.Park, and H.J.Kwon (2004).
A new curcumin derivative, HBC, interferes with the cell cycle progression of colon cancer cells via antagonization of the Ca2+/calmodulin function.
  Chem Biol, 11, 1455-1463.  
12890685 A.Popescu, S.Miron, Y.Blouquit, P.Duchambon, P.Christova, and C.T.Craescu (2003).
Xeroderma pigmentosum group C protein possesses a high affinity binding site to human centrin 2 and calmodulin.
  J Biol Chem, 278, 40252-40261.  
14597710 J.M.Shifman, and S.L.Mayo (2003).
Exploring the origins of binding specificity through the computational redesign of calmodulin.
  Proc Natl Acad Sci U S A, 100, 13274-13279.  
12846835 P.Prijatelj, J.Sribar, G.Ivanovski, I.Krizaj, F.Gubensek, and J.Pungercar (2003).
Identification of a novel binding site for calmodulin in ammodytoxin A, a neurotoxic group IIA phospholipase A2.
  Eur J Biochem, 270, 3018-3025.  
12542690 S.W.Vetter, and E.Leclerc (2003).
Novel aspects of calmodulin target recognition and activation.
  Eur J Biochem, 270, 404-414.  
12124297 M.L.Mattinen, K.Pääkkönen, T.Ikonen, J.Craven, T.Drakenberg, R.Serimaa, J.Waltho, and A.Annila (2002).
Quaternary structure built from subunits combining NMR and small-angle x-ray scattering data.
  Biophys J, 83, 1177-1183.  
11115624 G.M.Ananyev, L.Zaltsman, C.Vasko, and G.C.Dismukes (2001).
The inorganic biochemistry of photosynthetic oxygen evolution/water oxidation.
  Biochim Biophys Acta, 1503, 52-68.  
11685248 J.J.Chou, S.Li, C.B.Klee, and A.Bax (2001).
Solution structure of Ca(2+)-calmodulin reveals flexible hand-like properties of its domains.
  Nat Struct Biol, 8, 990-997.
PDB codes: 1j7o 1j7p
11129794 K.Gonda, M.Komatsu, and O.Numata (2000).
Calmodulin and Ca2+/calmodulin-binding proteins are involved in Tetrahymena thermophila phagocytosis.
  Cell Struct Funct, 25, 243-251.  
10618443 L.L.Pearce, R.E.Gandley, W.Han, K.Wasserloos, M.Stitt, A.J.Kanai, M.K.McLaughlin, B.R.Pitt, and E.S.Levitan (2000).
Role of metallothionein in nitric oxide signaling as revealed by a green fluorescent fusion protein.
  Proc Natl Acad Sci U S A, 97, 477-482.  
10792039 Y.Li, M.L.Love, J.A.Putkey, and C.Cohen (2000).
Bepridil opens the regulatory N-terminal lobe of cardiac troponin C.
  Proc Natl Acad Sci U S A, 97, 5140-5145.
PDB code: 1dtl
10608854 Z.Li, S.H.Kim, J.M.Higgins, M.B.Brenner, and D.B.Sacks (1999).
IQGAP1 and calmodulin modulate E-cadherin function.
  J Biol Chem, 274, 37885-37892.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

spacer
spacer