PDBsum entry 1mxe

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protein metals Protein-protein interface(s) links
Metal binding protein PDB id
Protein chains
144 a.a. *
25 a.a. *
_CA ×8
Waters ×234
* Residue conservation analysis
PDB id:
Name: Metal binding protein
Title: Structure of the complex of calmodulin with the target sequence of camki
Structure: Calmodulin. Chain: a, b. Engineered: yes. Target sequence of rat calmodulin-dependent protein kinase i. Chain: e, f. Fragment: calmodulin binding domain. Synonym: cam kinase i. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Synthetic: yes. Other_details: peptide synthesis
Biol. unit: Tetramer (from PQS)
1.70Å     R-factor:   0.190     R-free:   0.229
Authors: J.A.Clapperton,S.R.Martin,S.J.Smerdon,S.J.Gamblin,P.M.Bayley
Key ref:
J.A.Clapperton et al. (2002). Structure of the complex of calmodulin with the target sequence of calmodulin-dependent protein kinase I: studies of the kinase activation mechanism. Biochemistry, 41, 14669-14679. PubMed id: 12475216 DOI: 10.1021/bi026660t
02-Oct-02     Release date:   04-Dec-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P62152  (CALM_DROME) -  Calmodulin
149 a.a.
144 a.a.
Protein chains
Pfam   ArchSchema ?
Q63450  (KCC1A_RAT) -  Calcium/calmodulin-dependent protein kinase type 1
374 a.a.
25 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains E, F: E.C.  - Calcium/calmodulin-dependent protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
      Cofactor: Ca(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     midbody   9 terms 
  Biological process     photoreceptor cell axon guidance   17 terms 
  Biochemical function     myosin VI head/neck binding     7 terms  


DOI no: 10.1021/bi026660t Biochemistry 41:14669-14679 (2002)
PubMed id: 12475216  
Structure of the complex of calmodulin with the target sequence of calmodulin-dependent protein kinase I: studies of the kinase activation mechanism.
J.A.Clapperton, S.R.Martin, S.J.Smerdon, S.J.Gamblin, P.M.Bayley.
Calcium-saturated calmodulin (CaM) directly activates CaM-dependent protein kinase I (CaMKI) by binding to a region in the C-terminal regulatory sequence of the enzyme to relieve autoinhibition. The structure of CaM in a high-affinity complex with a 25-residue peptide of CaMKI (residues 294-318) has been determined by X-ray crystallography at 1.7 A resolution. Upon complex formation, the CaMKI peptide adopts an alpha-helical conformation, while changes in the CaM domain linker enable both its N- and C-domains to wrap around the peptide helix. Target peptide residues Trp-303 (interacting with the CaM C-domain) and Met-316 (with the CaM N-domain) define the mode of binding as 1-14. In addition, two basic patches on the peptide form complementary charge interactions with CaM. The CaM-peptide affinity is approximately 1 pM, compared with 30 nM for the CaM-kinase complex, indicating that activation of autoinhibited CaMKI by CaM requires a costly energetic disruption of the interactions between the CaM-binding sequence and the rest of the enzyme. We present biochemical and structural evidence indicating the involvement of both CaM domains in the activation process: while the C-domain exhibits tight binding toward the regulatory sequence, the N-domain is necessary for activation. Our crystal structure also enables us to identify the full CaM-binding sequence. Residues Lys-296 and Phe-298 from the target peptide interact directly with CaM, demonstrating overlap between the autoinhibitory and CaM-binding sequences. Thus, the kinase activation mechanism involves the binding of CaM to residues associated with the inhibitory pseudosubstrate sequence.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20686800 B.Holakovska, L.Grycova, J.Bily, and J.Teisinger (2011).
Characterization of calmodulin binding domains in TRPV2 and TRPV5 C-tails.
  Amino Acids, 40, 741-748.  
21360154 J.L.Gifford, H.Ishida, and H.J.Vogel (2011).
Fast methionine-based solution structure determination of calcium-calmodulin complexes.
  J Biomol NMR, 50, 71-81.
PDB code: 2l7l
20544963 M.D.Feldkamp, S.E.O'Donnell, L.Yu, and M.A.Shea (2010).
Allosteric effects of the antipsychotic drug trifluoperazine on the energetics of calcium binding by calmodulin.
  Proteins, 78, 2265-2282.  
20383153 M.S.Marlow, J.Dogan, K.K.Frederick, K.G.Valentine, and A.J.Wand (2010).
The role of conformational entropy in molecular recognition by calmodulin.
  Nat Chem Biol, 6, 352-358.  
19996092 N.Juranic, E.Atanasova, A.G.Filoteo, S.Macura, F.G.Prendergast, J.T.Penniston, and E.E.Strehler (2010).
Calmodulin wraps around its binding domain in the plasma membrane Ca2+ pump anchored by a novel 18-1 motif.
  J Biol Chem, 285, 4015-4024.
PDB code: 2kne
19998355 Y.Zhang, H.Tan, G.Chen, and Z.Jia (2010).
Investigating the disorder-order transition of calmodulin binding domain upon binding calmodulin using molecular dynamics simulation.
  J Mol Recognit, 23, 360-368.  
19416847 M.V.Vinogradova, G.G.Malanina, A.S.Reddy, and R.J.Fletterick (2009).
Structure of the complex of a mitotic kinesin with its calcium binding regulator.
  Proc Natl Acad Sci U S A, 106, 8175-8179.
PDB code: 3h4s
19137330 S.M.Mustafi, R.B.Mutalik, R.Jain, K.Chandra, A.Bhattacharya, and K.V.Chary (2009).
Structural characterization of a novel Ca2+-binding protein from Entamoeba histolytica: structural basis for the observed functional differences with its isoform.
  J Biol Inorg Chem, 14, 471-483.  
19089983 T.I.Evans, and M.A.Shea (2009).
Energetics of calmodulin domain interactions with the calmodulin binding domain of CaMKII.
  Proteins, 76, 47-61.  
19404396 V.Majava, and P.Kursula (2009).
Domain swapping and different oligomeric States for the complex between calmodulin and the calmodulin-binding domain of calcineurin a.
  PLoS ONE, 4, e5402.
PDB code: 2w73
19348766 Y.Zhou, W.Yang, M.M.Lurtz, Y.Chen, J.Jiang, Y.Huang, C.F.Louis, and J.J.Yang (2009).
Calmodulin mediates the Ca2+-dependent regulation of Cx44 gap junctions.
  Biophys J, 96, 2832-2848.  
19081058 Q.Wang, B.Shui, M.I.Kotlikoff, and H.Sondermann (2008).
Structural basis for calcium sensing by GCaMP2.
  Structure, 16, 1817-1827.
PDB codes: 3evp 3evr 3evu 3evv
18284662 V.Majava, M.V.Petoukhov, N.Hayashi, P.Pirilä, D.I.Svergun, and P.Kursula (2008).
Interaction between the C-terminal region of human myelin basic protein and calmodulin: analysis of complex formation and solution structure.
  BMC Struct Biol, 8, 10.  
18075575 K.Henzler-Wildman, and D.Kern (2007).
Dynamic personalities of proteins.
  Nature, 450, 964-972.  
17901047 Y.Zhou, W.Yang, M.M.Lurtz, Y.Ye, Y.Huang, H.W.Lee, Y.Chen, C.F.Louis, and J.J.Yang (2007).
Identification of the calmodulin binding domain of connexin 43.
  J Biol Chem, 282, 35005-35017.  
17027503 A.A.Maximciuc, J.A.Putkey, Y.Shamoo, and K.R.Mackenzie (2006).
Complex of calmodulin with a ryanodine receptor target reveals a novel, flexible binding mode.
  Structure, 14, 1547-1556.
PDB code: 2bcx
16568447 A.Ganoth, E.Nachliel, R.Friedman, and M.Gutman (2006).
Molecular dynamics study of a calmodulin-like protein with an IQ peptide: spontaneous refolding of the protein around the peptide.
  Proteins, 64, 133-146.  
16844751 A.Ganoth, R.Friedman, E.Nachliel, and M.Gutman (2006).
A molecular dynamics study and free energy analysis of complexes between the Mlc1p protein and two IQ motif peptides.
  Biophys J, 91, 2436-2450.  
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.  
16267044 L.Baekgaard, L.Luoni, M.I.De Michelis, and M.G.Palmgren (2006).
The plant plasma membrane Ca2+ pump ACA8 contains overlapping as well as physically separated autoinhibitory and calmodulin-binding domains.
  J Biol Chem, 281, 1058-1065.  
16945920 M.Simonovic, Z.Zhang, C.D.Cianci, T.A.Steitz, and J.S.Morrow (2006).
Structure of the calmodulin alphaII-spectrin complex provides insight into the regulation of cell plasticity.
  J Biol Chem, 281, 34333-34340.
PDB code: 2fot
15752366 A.G.Cook, L.N.Johnson, and J.M.McDonnell (2005).
Structural characterization of Ca2+/CaM in complex with the phosphorylase kinase PhK5 peptide.
  FEBS J, 272, 1511-1522.  
16319880 S.McLaughlin, and D.Murray (2005).
Plasma membrane phosphoinositide organization by protein electrostatics.
  Nature, 438, 605-611.  
14670974 A.P.Yamniuk, and H.J.Vogel (2004).
Structurally homologous binding of plant calmodulin isoforms to the calmodulin-binding domain of vacuolar calcium-ATPase.
  J Biol Chem, 279, 7698-7707.  
14980206 W.Zhou, Y.Qian, K.Kunjilwar, P.J.Pfaffinger, and S.Choe (2004).
Structural insights into the functional interaction of KChIP1 with Shal-type K(+) channels.
  Neuron, 41, 573-586.
PDB code: 1s6c
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.