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PDBsum entry 1qiw

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protein ligands metals Protein-protein interface(s) links
Calcium-binding protein PDB id
1qiw
Jmol
Contents
Protein chains
145 a.a. *
Ligands
DPD ×3
Metals
_CA ×8
* Residue conservation analysis
PDB id:
1qiw
Name: Calcium-binding protein
Title: Calmodulin complexed with n-(3,3,-diphenylpropyl)-n'-[1-r-( 3,4-bis-butoxyphenyl)-ethyl]-propylenediamine (dpd)
Structure: Calmodulin. Chain: a, b
Source: Bos taurus. Bovine. Organism_taxid: 9913. Organ: brain. Cellular_location: cytoplasm
Resolution:
2.30Å     R-factor:   0.232     R-free:   0.317
Authors: V.Harmat,Z.S.Bocskei,B.G.Vertessy,J.Ovadi,G.Naray-Szabo
Key ref:
V.Harmat et al. (2000). A new potent calmodulin antagonist with arylalkylamine structure: crystallographic, spectroscopic and functional studies. J Mol Biol, 297, 747-755. PubMed id: 10731425 DOI: 10.1006/jmbi.2000.3607
Date:
17-Jun-99     Release date:   28-Mar-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P62157  (CALM_BOVIN) -  Calmodulin
Seq:
Struc:
149 a.a.
145 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   9 terms 
  Biological process     regulation of cytokinesis   12 terms 
  Biochemical function     ion channel binding     10 terms  

 

 
DOI no: 10.1006/jmbi.2000.3607 J Mol Biol 297:747-755 (2000)
PubMed id: 10731425  
 
 
A new potent calmodulin antagonist with arylalkylamine structure: crystallographic, spectroscopic and functional studies.
V.Harmat, Z.Böcskei, G.Náray-Szabó, I.Bata, A.S.Csutor, I.Hermecz, P.Arányi, B.Szabó, K.Liliom, B.G.Vértessy, J.Ovádi.
 
  ABSTRACT  
 
An arylalkylamine-type calmodulin antagonist, N-(3, 3-diphenylpropyl)-N'-[1-R-(3, 4-bis-butoxyphenyl)ethyl]-propylene-diamine (AAA) is presented and its complexes with calmodulin are characterized in solution and in the crystal. Near-UV circular dichroism spectra show that AAA binds to calmodulin with 2:1 stoichiometry in a Ca(2+)-dependent manner. The crystal structure with 2:1 stoichiometry is determined to 2.64 A resolution. The binding of AAA causes domain closure of calmodulin similar to that obtained with trifluoperazine. Solution and crystal data indicate that each of the two AAA molecules anchors in the hydrophobic pockets of calmodulin, overlapping with two trifluoperazine sites, i.e. at a hydrophobic pocket and an interdomain site. The two AAA molecules also interact with each other by hydrophobic forces. A competition enzymatic assay has revealed that AAA inhibits calmodulin-activated phosphodiesterase activity at two orders of magnitude lower concentration than trifluoperazine. The apparent dissociation constant of AAA to calmodulin is 18 nM, which is commensurable with that of target peptides. On the basis of the crystal structure, we propose that the high-affinity binding is mainly due to a favorable entropy term, as the AAA molecule makes multiple contacts in its complex with calmodulin.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Structural details of AAA binding in the crystal structure. (a) Stereo view of (2F[o] -F[c]) electron density map contoured at the 1s level around the AAA binding sites. Carbon atoms of the AAAs are colored magenta while AAAs and methionine residues are labeled. (b) Comparison of the binding sites of AAA molecules. AAA1 (left) and AAA2 (right) (lines and circles) are shown with the interacting protein residues (lines). The orientation of CaM is changed between the left and right panels by fitting backbone atoms of the two domains onto each other considering the similar fold of those. The accommodations and conformations of the two AAAs are very similar. (c) The backbone conformation of CaM colored from the N-terminal to the C-terminal from blue to red with the two bound AAA molecules. (d) Comparison of the P3[2]21 crystal structure (red) with the P1 structure (green). The conformation of AAA changes upon the domain motion of CaM. AAA2 and the interacting helices of the N-terminal domain are shown with the C^a atoms of residues 92 to 144 fitted together. The molecular surface of the C-terminal hydrophobic pocket of CaM, calculated by GRASP [Nicholls et al 1991], is shown as a chicken-wire representation (blue). The most important interactions between AAA and CaM, shown only for P3[2]21, are emphasized with yellow shaded lines. The black arrow shows the change in conformation of AAA2 following the domain motion of CaM. (a) Drawn with Bobscript v2.3 [Esnouf 1997] and (b), (c) and (d) with MOLSCRIPT v2.1 [Kraulis 1991].
Figure 6.
Figure 6. Comparison of the AAA and TFP-binding sites of CaM. The four TFP-binding sites, as found by [Vandonselaar et al 1994], are shown as shaded ellipses and labeled T1-T4. Considering the structural similarity of the two domains, two other sites (similar to T2 and T3) can be imagined, T5 and T6 (empty ellipses).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 297, 747-755) copyright 2000.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21514702 A.Reyes-Ramírez, M.Leyte-Lugo, M.Figueroa, T.Serrano-Alba, M.González-Andrade, and R.Mata (2011).
Synthesis, biological evaluation, and docking studies of gigantol analogs as calmodulin inhibitors.
  Eur J Med Chem, 46, 2699-2708.  
19280122 S.J.Abraham, T.Kobayashi, R.J.Solaro, and V.Gaponenko (2009).
Differences in lysine pKa values may be used to improve NMR signal dispersion in reductively methylated proteins.
  J Biomol NMR, 43, 239-246.  
16967519 A.O.Omoni, and R.E.Aluko (2006).
Effect of cationic flaxseed protein hydrolysate fractions on the in vitro structure and activity of calmodulin-dependent endothelial nitric oxide synthase.
  Mol Nutr Food Res, 50, 958-966.  
16721661 K.Chen, J.Ruan, and L.A.Kurgan (2006).
Prediction of three dimensional structure of calmodulin.
  Protein J, 25, 57-70.  
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
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.  
14765114 M.Matsubara, T.Nakatsu, H.Kato, and H.Taniguchi (2004).
Crystal structure of a myristoylated CAP-23/NAP-22 N-terminal domain complexed with Ca2+/calmodulin.
  EMBO J, 23, 712-718.
PDB code: 1l7z
12577052 E.Yamauchi, T.Nakatsu, M.Matsubara, H.Kato, and H.Taniguchi (2003).
Crystal structure of a MARCKS peptide containing the calmodulin-binding domain in complex with Ca2+-calmodulin.
  Nat Struct Biol, 10, 226-231.
PDB code: 1iwq
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.