PDBsum entry 1smg

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Calcium-binding protein PDB id
Protein chain
90 a.a. *
* Residue conservation analysis
PDB id:
Name: Calcium-binding protein
Title: Calcium-bound e41a mutant of the n-domain of chicken troponin c, nmr, 40 structures
Structure: Troponin c. Chain: a. Fragment: n-domain. Synonym: tnc. Engineered: yes. Mutation: yes. Other_details: 2 calcium ions bound in solution
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Cell_line: bl21. Organ: skeletal. Tissue: muscle. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 40 models
Authors: S.M.Gagne,M.X.Li,B.D.Sykes
Key ref:
S.M.Gagné et al. (1997). Mechanism of direct coupling between binding and induced structural change in regulatory calcium binding proteins. Biochemistry, 36, 4386-4392. PubMed id: 9109645 DOI: 10.1021/bi963076+
04-Feb-97     Release date:   12-Aug-97    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P02588  (TNNC2_CHICK) -  Troponin C, skeletal muscle
163 a.a.
90 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     calcium ion binding     1 term  


DOI no: 10.1021/bi963076+ Biochemistry 36:4386-4392 (1997)
PubMed id: 9109645  
Mechanism of direct coupling between binding and induced structural change in regulatory calcium binding proteins.
S.M.Gagné, M.X.Li, B.D.Sykes.
The structural transition in troponin C induced by the binding of two calcium ions involves an "opening" of the structure, an event that triggers skeletal muscle contraction. We have solved the solution structure of a mutant (E41A) of the regulatory domain of skeletal troponin C wherein one bidentate ligand to the calcium in site I is missing. This structure remains "closed" upon calcium binding, indicating that the linkage between calcium binding and the induced conformational change has been broken. This provides a snapshot of skeletal troponin C between the off and on state and thereby valuable insight into the mechanism of regulation within skeletal TnC. Although several factors contribute to the triggering mechanism, the opening of the troponin C structure is ultimately dependent on one amino acid, Glu41. Insights into the structure of cardiac troponin C can also be derived from this skeletal mutant.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21269277 L.Santamaria-Kisiel, and G.S.Shaw (2011).
Identification of regions responsible for the open conformation of S100A10 using chimaeric S100A11-S100A10 proteins.
  Biochem J, 434, 37-48.  
21262274 Z.Grabarek (2011).
Insights into modulation of calcium signaling by magnesium in calmodulin, troponin C and related EF-hand proteins.
  Biochim Biophys Acta, 1813, 913-921.  
20048169 L.W.Xiong, Q.K.Kleerekoper, X.Wang, and J.A.Putkey (2010).
Intra- and interdomain effects due to mutation of calcium-binding sites in calmodulin.
  J Biol Chem, 285, 8094-8103.  
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
19297189 S.L.Shirran, and P.E.Barran (2009).
The use of ESI-MS to probe the binding of divalent cations to calmodulin.
  J Am Soc Mass Spectrom, 20, 1159-1171.  
18339805 C.N.Chi, L.Elfström, Y.Shi, T.Snäll, A.Engström, and P.Jemth (2008).
Reassessing a sparse energetic network within a single protein domain.
  Proc Natl Acad Sci U S A, 105, 4679-4684.  
18689462 M.C.Suarez, C.B.Rocha, M.M.Sorenson, J.L.Silva, and D.Foguel (2008).
Free-energy linkage between folding and calcium binding in EF-hand proteins.
  Biophys J, 95, 4820-4828.  
16957918 F.Capozzi, F.Casadei, and C.Luchinat (2006).
EF-hand protein dynamics and evolution of calcium signal transduction: an NMR view.
  J Biol Inorg Chem, 11, 949-962.  
15826946 T.M.Blumenschein, D.B.Stone, R.J.Fletterick, R.A.Mendelson, and B.D.Sykes (2005).
Calcium-dependent changes in the flexibility of the regulatory domain of troponin C in the troponin complex.
  J Biol Chem, 280, 21924-21932.  
14990485 I.Marcotte, F.Separovic, M.Auger, and S.M.Gagné (2004).
A multidimensional 1H NMR investigation of the conformation of methionine-enkephalin in fast-tumbling bicelles.
  Biophys J, 86, 1587-1600.
PDB codes: 1plw 1plx
12732641 D.A.Lindhout, and B.D.Sykes (2003).
Structure and dynamics of the C-domain of human cardiac troponin C in complex with the inhibitory region of human cardiac troponin I.
  J Biol Chem, 278, 27024-27034.
PDB code: 1ozs
12531902 F.F.Valencia, A.A.Paulucci, R.B.Quaggio, A.C.Da Silva, C.S.Farah, and F.C.Reinach (2003).
Parallel measurement of Ca2+ binding and fluorescence emission upon Ca2+ titration of recombinant skeletal muscle troponin C. Measurement of sequential calcium binding to the regulatory sites.
  J Biol Chem, 278, 11007-11014.  
12524267 F.Pitici (2003).
Structural preference for changes in the direction of the Ca2+-induced transition: a study of the regulatory domain of skeletal troponin-C.
  Biophys J, 84, 82.  
12022873 S.B.Tikunova, J.A.Rall, and J.P.Davis (2002).
Effect of hydrophobic residue substitutions with glutamine on Ca(2+) binding and exchange with the N-domain of troponin C.
  Biochemistry, 41, 6697-6705.  
12060657 X.Wang, M.X.Li, and B.D.Sykes (2002).
Structure of the regulatory N-domain of human cardiac troponin C in complex with human cardiac troponin I147-163 and bepridil.
  J Biol Chem, 277, 31124-31133.
PDB code: 1lxf
11266616 A.Ababou, and J.R.Desjarlais (2001).
Solvation energetics and conformational change in EF-hand proteins.
  Protein Sci, 10, 301-312.  
11119639 B.V.Reddy, W.W.Li, I.N.Shindyalov, and P.E.Bourne (2001).
Conserved key amino acid positions (CKAAPs) derived from the analysis of common substructures in proteins.
  Proteins, 42, 148-163.  
11562942 T.Kesvatera, B.Jönsson, E.Thulin, and S.Linse (2001).
Focusing of the electrostatic potential at EF-hands of calbindin D(9k): titration of acidic residues.
  Proteins, 45, 129-135.  
10951187 D.H.MacLennan (2000).
Ca2+ signalling and muscle disease.
  Eur J Biochem, 267, 5291-5297.  
10766953 R.Oliva, L.Falcigno, G.D'Auria, M.Saviano, L.Paolillo, G.Ansanelli, and G.Zanotti (2000).
Bicyclic peptides as models of calcium binding sites: synthesis and conformation of a homodetic undecapeptide.
  Biopolymers, 53, 581-595.  
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
10471276 B.Whitehead, M.Tessari, A.Carotenuto, P.M.van Bergen en Henegouwen, and G.W.Vuister (1999).
The EH1 domain of Eps15 is structurally classified as a member of the S100 subclass of EF-hand-containing proteins.
  Biochemistry, 38, 11271-11277.
PDB code: 1qjt
10531339 W.J.Dong, J.Xing, M.Villain, M.Hellinger, J.M.Robinson, M.Chandra, R.J.Solaro, P.K.Umeda, and H.C.Cheung (1999).
Conformation of the regulatory domain of cardiac muscle troponin C in its complex with cardiac troponin I.
  J Biol Chem, 274, 31382-31390.  
9786904 A.Malmendal, J.Evenäs, E.Thulin, G.P.Gippert, T.Drakenberg, and S.Forsén (1998).
When size is important. Accommodation of magnesium in a calcium binding regulatory domain.
  J Biol Chem, 273, 28994-29001.  
9753463 J.Evenäs, A.Malmendal, E.Thulin, G.Carlström, and S.Forsén (1998).
Ca2+ binding and conformational changes in a calmodulin domain.
  Biochemistry, 37, 13744-13754.  
9667926 J.Evenäs, A.Malmendal, and S.Forsén (1998).
  Curr Opin Chem Biol, 2, 293-302.  
9636033 K.Julenius, E.Thulin, S.Linse, and B.E.Finn (1998).
Hydrophobic core substitutions in calbindin D9k: effects on stability and structure.
  Biochemistry, 37, 8915-8925.  
9624156 K.Pääkkönen, A.Annila, T.Sorsa, P.Pollesello, C.Tilgmann, I.Kilpeläinen, P.Karisola, I.Ulmanen, and T.Drakenberg (1998).
Solution structure and main chain dynamics of the regulatory domain (Residues 1-91) of human cardiac troponin C.
  J Biol Chem, 273, 15633-15638.  
9922172 L.Spyracopoulos, S.M.Gagné, M.X.Li, and B.D.Sykes (1998).
Dynamics and thermodynamics of the regulatory domain of human cardiac troponin C in the apo- and calcium-saturated states.
  Biochemistry, 37, 18032-18044.  
  9521102 M.R.Nelson, and W.J.Chazin (1998).
An interaction-based analysis of calcium-induced conformational changes in Ca2+ sensor proteins.
  Protein Sci, 7, 270-282.  
9585577 R.R.Biekofsky, S.R.Martin, J.P.Browne, P.M.Bayley, and J.Feeney (1998).
Ca2+ coordination to backbone carbonyl oxygen atoms in calmodulin and other EF-hand proteins: 15N chemical shifts as probes for monitoring individual-site Ca2+ coordination.
  Biochemistry, 37, 7617-7629.  
9730814 R.T.McKay, J.R.Pearlstone, D.C.Corson, S.M.Gagné, L.B.Smillie, and B.D.Sykes (1998).
Structure and interaction site of the regulatory domain of troponin-C when complexed with the 96-148 region of troponin-I.
  Biochemistry, 37, 12419-12430.
PDB code: 1blq
9519411 S.P.Smith, and G.S.Shaw (1998).
A novel calcium-sensitive switch revealed by the structure of human S100B in the calcium-bound form.
  Structure, 6, 211-222.
PDB code: 1uwo
9517413 Y.Ohizumi, K.Matsunaga, K.Nakatani, and J.Kobayashi (1998).
The powerful stimulatory action of 6-O-acetyl-9-methyl-7-bromoeudistomin D on the contractile protein system of rabbit skeletal muscle.
  Jpn J Pharmacol, 76, 113-116.  
9315850 L.Spyracopoulos, M.X.Li, S.K.Sia, S.M.Gagné, M.Chandra, R.J.Solaro, and B.D.Sykes (1997).
Calcium-induced structural transition in the regulatory domain of human cardiac troponin C.
  Biochemistry, 36, 12138-12146.
PDB codes: 1ap4 1spy
9218458 S.K.Sia, M.X.Li, L.Spyracopoulos, S.M.Gagné, W.Liu, J.A.Putkey, and B.D.Sykes (1997).
Structure of cardiac muscle troponin C unexpectedly reveals a closed regulatory domain.
  J Biol Chem, 272, 18216-18221.
PDB codes: 1aj4 2ctn 3ctn
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.