PDBsum entry 1k8u

Go to PDB code: 
protein links
Signaling protein PDB id
Protein chain
89 a.a. *
Waters ×117
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Crystal structure of calcium-free (or apo) human s100a6; cys mutant (selenomethionine derivative)
Structure: S100a6. Chain: a. Synonym: calcyclin, cacy. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
1.15Å     R-factor:   0.186     R-free:   0.221
Authors: L.R.Otterbein,R.Dominguez
Key ref:
L.R.Otterbein et al. (2002). Crystal structures of S100A6 in the Ca(2+)-free and Ca(2+)-bound states: the calcium sensor mechanism of S100 proteins revealed at atomic resolution. Structure, 10, 557-567. PubMed id: 11937060 DOI: 10.1016/S0969-2126(02)00740-2
25-Oct-01     Release date:   10-Apr-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P06703  (S10A6_HUMAN) -  Protein S100-A6
90 a.a.
89 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!
  Cellular component     membrane   10 terms 
  Biological process     signal transduction   4 terms 
  Biochemical function     S100 protein binding     9 terms  


DOI no: 10.1016/S0969-2126(02)00740-2 Structure 10:557-567 (2002)
PubMed id: 11937060  
Crystal structures of S100A6 in the Ca(2+)-free and Ca(2+)-bound states: the calcium sensor mechanism of S100 proteins revealed at atomic resolution.
L.R.Otterbein, J.Kordowska, C.Witte-Hoffmann, C.L.Wang, R.Dominguez.
S100A6 is a member of the S100 family of Ca(2+) binding proteins, which have come to play an important role in the diagnosis of cancer due to their overexpression in various tumor cells. We have determined the crystal structures of human S100A6 in the Ca(2+)-free and Ca(2+)-bound states to resolutions of 1.15 A and 1.44 A, respectively. Ca(2+) binding is responsible for a dramatic change in the global shape and charge distribution of the S100A6 dimer, leading to the exposure of two symmetrically positioned target binding sites. The results are consistent with S100A6, and most likely other S100 proteins, functioning as Ca(2+) sensors in a way analogous to the prototypical sensors calmodulin and troponin C. The structures have important implications for our understanding of target binding and cooperativity of Ca(2+) binding in the S100 family.
  Selected figure(s)  
Figure 3.
Figure 3. Electrostatic Surface Representation of the S100A6 Dimers in the Ca^2+-Free and Ca^2+-Bound StatesThe full-charge electrostatic potential calculation was performed with program GRASP [50]. Red and blue areas indicate negatively and positively charged regions, respectively. Three views of the molecules are shown for each state rotated in increments of 90 (A and B). Notice how the electrostatic charge distribution on one side of the molecule (facing helices I and I') is less dramatically affected than the opposite side (facing helices IV and IV') by Ca^2+ binding. Thus, Ca^2+-bound S1006 can be clearly distinguished from its Ca^2+-free counterpart as a globally more hydrophobic state. Notice also how Ca^2+ binding brings about marked changes in the shape of the molecule, creating two symmetrically positioned target binding sites (see also Figure 4). The Ca^2+-bound dimer exposes a surface of 9549 2 to the solvent as compared to 9136 2 for the Ca^2+-free state.
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 557-567) copyright 2002.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21283550 C.Tuzmen, and B.Erman (2011).
Identification of ligand binding sites of proteins using the gaussian network model.
  PLoS One, 6, e16474.  
21046186 E.Babini, I.Bertini, V.Borsi, V.Calderone, X.Hu, C.Luchinat, and G.Parigi (2011).
Structural characterization of human S100A16, a low-affinity calcium binder.
  J Biol Inorg Chem, 16, 243-256.
PDB codes: 2l50 2l51 3nxa
21132840 J.R.Perilla, O.Beckstein, E.J.Denning, and T.B.Woolf (2011).
Computing ensembles of transitions from stable states: Dynamic importance sampling.
  J Comput Chem, 32, 196-209.  
  20827422 D.B.Zimmer, and D.J.Weber (2010).
The Calcium-Dependent Interaction of S100B with Its Protein Targets.
  Cardiovasc Psychiatry Neurol, 2010, 0.  
20439752 E.T.Petri, A.Celic, S.D.Kennedy, B.E.Ehrlich, T.J.Boggon, and M.E.Hodsdon (2010).
Structure of the EF-hand domain of polycystin-2 suggests a mechanism for Ca2+-dependent regulation of polycystin-2 channel activity.
  Proc Natl Acad Sci U S A, 107, 9176-9181.
PDB code: 2kq6
20053360 T.H.Charpentier, L.E.Thompson, M.A.Liriano, K.M.Varney, P.T.Wilder, E.Pozharski, E.A.Toth, and D.J.Weber (2010).
The effects of CapZ peptide (TRTK-12) binding to S100B-Ca2+ as examined by NMR and X-ray crystallography.
  J Mol Biol, 396, 1227-1243.
PDB codes: 3iqo 3iqq
19712129 A.Ishii, M.Suzuki, K.Satomi, H.Kobayashi, S.Sakashita, J.Kano, Y.Pei, Y.Minami, S.Ishikawa, and M.Noguchi (2009).
Increased cytoplasmic S100A6 expression is associated with pulmonary adenocarcinoma progression.
  Pathol Int, 59, 623-630.  
19604472 D.S.Glazer, R.J.Radmer, and R.B.Altman (2009).
Improving structure-based function prediction using molecular dynamics.
  Structure, 17, 919-929.  
19536568 I.Bertini, S.Das Gupta, X.Hu, T.Karavelas, C.Luchinat, G.Parigi, and J.Yuan (2009).
Solution structure and dynamics of S100A5 in the apo and Ca2+-bound states.
  J Biol Inorg Chem, 14, 1097-1107.
PDB codes: 2kax 2kay
  19890475 N.T.Wright, B.R.Cannon, D.B.Zimmer, and D.J.Weber (2009).
S100A1: Structure, Function, and Therapeutic Potential.
  Curr Chem Biol, 3, 138-145.  
  18259052 F.L.Imai, K.Nagata, N.Yonezawa, M.Nakano, and M.Tanokura (2008).
Structure of calcium-bound human S100A13 at pH 7.5 at 1.8 A resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 70-76.
PDB code: 2egd
17721932 J.H.Joo, S.Y.Yoon, J.H.Kim, S.G.Paik, S.R.Min, J.S.Lim, I.S.Choe, I.Choi, and J.W.Kim (2008).
S100A6 (calcyclin) enhances the sensitivity to apoptosis via the upregulation of caspase-3 activity in Hep3B cells.
  J Cell Biochem, 103, 1183-1197.  
18783790 P.Pathuri, L.Vogeley, and H.Luecke (2008).
Crystal structure of metastasis-associated protein S100A4 in the active calcium-bound form.
  J Mol Biol, 383, 62-77.
PDB code: 3cga
18384084 S.Malik, M.Revington, S.P.Smith, and G.S.Shaw (2008).
Analysis of the structure of human apo-S100B at low temperature indicates a unimodal conformational distribution is adopted by calcium-free S100 proteins.
  Proteins, 73, 28-42.
PDB code: 2pru
18602402 T.H.Charpentier, P.T.Wilder, M.A.Liriano, K.M.Varney, E.Pozharski, A.D.MacKerell, A.Coop, E.A.Toth, and D.J.Weber (2008).
Divalent metal ion complexes of S100B in the absence and presence of pentamidine.
  J Mol Biol, 382, 56-73.
PDB codes: 3cr2 3cr4 3cr5
18410126 V.N.Malashkevich, K.M.Varney, S.C.Garrett, P.T.Wilder, D.Knight, T.H.Charpentier, U.A.Ramagopal, S.C.Almo, D.J.Weber, and A.R.Bresnick (2008).
Structure of Ca2+-bound S100A4 and its interaction with peptides derived from nonmuscle myosin-IIA.
  Biochemistry, 47, 5111-5126.
PDB code: 2q91
18803400 Y.T.Lee, Y.N.Dimitrova, G.Schneider, W.B.Ridenour, S.Bhattacharya, S.E.Soss, R.M.Caprioli, A.Filipek, and W.J.Chazin (2008).
Structure of the S100A6 complex with a fragment from the C-terminal domain of Siah-1 interacting protein: a novel mode for S100 protein target recognition.
  Biochemistry, 47, 10921-10932.
PDB code: 2jtt
17158877 J.Xie, D.S.Burz, W.He, I.B.Bronstein, I.Lednev, and A.Shekhtman (2007).
Hexameric calgranulin C (S100A12) binds to the receptor for advanced glycated end products (RAGE) using symmetric hydrophobic target-binding patches.
  J Biol Chem, 282, 4218-4231.  
17499048 M.J.Sánchez-Barrena, H.Fujii, I.Angulo, M.Martínez-Ripoll, J.K.Zhu, and A.Albert (2007).
The structure of the C-terminal domain of the protein kinase AtSOS2 bound to the calcium sensor AtSOS3.
  Mol Cell, 26, 427-435.
PDB code: 2ehb
17970874 Y.Q.Yang, L.J.Zhang, H.Dong, C.L.Jiang, Z.G.Zhu, J.X.Wu, Y.L.Wu, J.S.Han, H.S.Xiao, H.J.Gao, and Q.H.Zhang (2007).
Upregulated expression of S100A6 in human gastric cancer.
  J Dig Dis, 8, 186-193.  
  16682778 K.M.Boeshans, R.Wolf, C.Voscopoulos, W.Gillette, D.Esposito, T.C.Mueser, S.H.Yuspa, and B.Ahvazi (2006).
Purification, crystallization and preliminary X-ray diffraction of human S100A15.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 467-470.  
  17077493 M.Koch, J.Diez, and G.Fritz (2006).
Purification and crystallization of the human EF-hand tumour suppressor protein S100A2.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 1120-1123.  
16145699 F.Arnesano, L.Banci, I.Bertini, A.Fantoni, L.Tenori, and M.S.Viezzoli (2005).
Structural interplay between calcium(II) and copper(II) binding to S100A13 protein.
  Angew Chem Int Ed Engl, 44, 6341-6344.
PDB codes: 1yur 1yus 1yut 1yuu
15927886 N.Leukert, C.Sorg, and J.Roth (2005).
Molecular basis of the complex formation between the two calcium-binding proteins S100A8 (MRP8) and S100A9 (MRP14).
  Biol Chem, 386, 429-434.  
12842051 A.C.Dempsey, M.P.Walsh, and G.S.Shaw (2003).
Unmasking the annexin I interaction from the structure of Apo-S100A11.
  Structure, 11, 887-897.
PDB code: 1nsh
12645003 D.B.Zimmer, P.Wright Sadosky, and D.J.Weber (2003).
Molecular mechanisms of S100-target protein interactions.
  Microsc Res Tech, 60, 552-559.  
12480931 K.A.McClintock, and G.S.Shaw (2003).
A novel S100 target conformation is revealed by the solution structure of the Ca2+-S100B-TRTK-12 complex.
  J Biol Chem, 278, 6251-6257.
PDB code: 1mq1
12777802 O.V.Moroz, A.A.Antson, S.J.Grist, N.J.Maitland, G.G.Dodson, K.S.Wilson, E.Lukanidin, and I.B.Bronstein (2003).
Structure of the human S100A12-copper complex: implications for host-parasite defence.
  Acta Crystallogr D Biol Crystallogr, 59, 859-867.
PDB code: 1odb
12136135 P.R.Mittl, G.Fritz, D.F.Sargent, T.J.Richmond, C.W.Heizmann, and M.G.Grütter (2002).
Metal-free MIRAS phasing: structure of apo-S100A3.
  Acta Crystallogr D Biol Crystallogr, 58, 1255-1261.
PDB code: 1kso
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 codes are shown on the right.