PDBsum entry 1esf

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Enterotoxin PDB id
Protein chains
229 a.a. *
_CD ×2
Waters ×168
* Residue conservation analysis
PDB id:
Name: Enterotoxin
Title: Staphylococcal enterotoxin a
Structure: Staphylococcal enterotoxin a. Chain: a, b. Engineered: yes
Source: Staphylococcus aureus. Organism_taxid: 1280. Expressed in: escherichia coli. Expression_system_taxid: 562
1.90Å     R-factor:   0.204     R-free:   0.277
Authors: E.M.Schad,L.A.Svensson
Key ref: E.M.Schad et al. (1995). Crystal structure of the superantigen staphylococcal enterotoxin type A. EMBO J, 14, 3292-3301. PubMed id: 7628431
25-May-95     Release date:   11-Jul-96    
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Protein chains
Pfam   ArchSchema ?
P0A0L2  (ETXA_STAAU) -  Enterotoxin type A
257 a.a.
229 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     pathogenesis   1 term 
  Biochemical function     metal ion binding     2 terms  


EMBO J 14:3292-3301 (1995)
PubMed id: 7628431  
Crystal structure of the superantigen staphylococcal enterotoxin type A.
E.M.Schad, I.Zaitseva, V.N.Zaitsev, M.Dohlsten, T.Kalland, P.M.Schlievert, D.H.Ohlendorf, L.A.Svensson.
Staphylococcal enterotoxins are prototype superantigens characterized by their ability to bind to major histocompatibility complex (MHC) class II molecules and subsequently activate a large fraction of T-lymphocytes. The crystal structure of staphylococcal enterotoxin type A (SEA), a 27 kDa monomeric protein, was determined to 1.9 A resolution with an R-factor of 19.9% by multiple isomorphous replacement. SEA is a two domain protein composed of a beta-barrel and a beta-grasp motif demonstrating the same general structure as staphylococcal enterotoxins SEB and TSST-1. Unique for SEA, however, is a Zn2+ coordination site involved in MHC class II binding. Four amino acids including Ser1, His187, His225 and Asp227 were found to be involved in direct coordination of the metal ion. SEA is the first Zn2+ binding enterotoxin that has been structurally determined.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21442364 I.Sospedra, C.Soler, J.Mañes, and J.M.Soriano (2011).
Analysis of staphylococcal enterotoxin A in milk by matrix-assisted laser desorption/ionization-time of flight mass spectrometry.
  Anal Bioanal Chem, 400, 1525-1531.  
21255209 S.J.Li, D.L.Hu, E.K.Maina, K.Shinagawa, K.Omoe, and A.Nakane (2011).
Superantigenic activity of toxic shock syndrome toxin-1 is resistant to heating and digestive enzymes.
  J Appl Microbiol, 110, 729-736.  
21176153 B.Drozdowski, Y.Zhou, B.Kline, J.Spidel, Y.Y.Chan, E.Albone, H.Turchin, Q.Chao, M.Henry, J.Balogach, E.Routhier, S.Bavari, N.C.Nicolaides, P.M.Sass, and L.Grasso (2010).
Generation and characterization of high affinity human monoclonal antibodies that neutralize staphylococcal enterotoxin B.
  J Immune Based Ther Vaccines, 8, 9.  
19133806 D.L.Hu, K.Omoe, H.Sashinami, K.Shinagawa, and A.Nakane (2009).
Immunization with a Nontoxic Mutant of Staphylococcal Enterotoxin A, SEAD227A, Protects against Enterotoxin-Induced Emesis in House Musk Shrews.
  J Infect Dis, 199, 302-310.  
19587800 K.Narayan, E.M.Perkins, G.E.Murphy, S.K.Dalai, M.Edidin, S.Subramaniam, and S.Sadegh-Nasseri (2009).
Staphylococcal enterotoxin A induces small clusters of HLA-DR1 on B cells.
  PLoS One, 4, e6188.  
19296099 X.Wang, H.Zhang, M.Xu, C.Liu, and C.Zhang (2009).
Biological analysis of the deletion mutants of Staphylococcal enterotoxin C2.
  Appl Microbiol Biotechnol, 83, 1077-1084.  
19246739 X.Wang, H.Zhang, M.Xu, Y.Cai, C.Liu, Z.Su, and C.Zhang (2009).
Biological characterization of the zinc site coordinating histidine residues of staphylococcal enterotoxin C2.
  Microbiology, 155, 680-686.  
19082587 X.Wang, M.Xu, Y.Cai, H.Yang, H.Zhang, and C.Zhang (2009).
Functional analysis of the disulphide loop mutant of staphylococcal enterotoxin C2.
  Appl Microbiol Biotechnol, 82, 861-871.  
16829512 M.M.Fernández, R.Guan, C.P.Swaminathan, E.L.Malchiodi, and R.A.Mariuzza (2006).
Crystal structure of staphylococcal enterotoxin I (SEI) in complex with a human major histocompatibility complex class II molecule.
  J Biol Chem, 281, 25356-25364.
PDB code: 2g9h
17078814 T.Bae, T.Baba, K.Hiramatsu, and O.Schneewind (2006).
Prophages of Staphylococcus aureus Newman and their contribution to virulence.
  Mol Microbiol, 62, 1035-1047.  
14559915 A.C.Papageorgiou, M.D.Baker, J.D.McLeod, S.K.Goda, C.N.Manzotti, D.M.Sansom, H.S.Tranter, and K.R.Acharya (2004).
Identification of a secondary zinc-binding site in staphylococcal enterotoxin C2. Implications for superantigen recognition.
  J Biol Chem, 279, 1297-1303.
PDB code: 1uns
15247241 H.M.Baker, T.Proft, P.D.Webb, V.L.Arcus, J.D.Fraser, and E.N.Baker (2004).
Crystallographic and mutational data show that the streptococcal pyrogenic exotoxin J can use a common binding surface for T-cell receptor binding and dimerization.
  J Biol Chem, 279, 38571-38576.
PDB codes: 1ty0 1ty2
15049778 K.Petersson, G.Forsberg, and B.Walse (2004).
Interplay between superantigens and immunoreceptors.
  Scand J Immunol, 59, 345-355.  
12676930 M.A.Langlois, Y.El Fakhry, and W.Mourad (2003).
Zinc-binding sites in the N terminus of Mycoplasma arthritidis-derived mitogen permit the dimer formation required for high affinity binding to HLA-DR and for T cell activation.
  J Biol Chem, 278, 22309-22315.  
12704169 P.M.Orwin, J.R.Fitzgerald, D.Y.Leung, J.A.Gutierrez, G.A.Bohach, and P.M.Schlievert (2003).
Characterization of Staphylococcus aureus enterotoxin L.
  Infect Immun, 71, 2916-2919.  
11847286 H.I.Krupka, B.W.Segelke, R.G.Ulrich, S.Ringhofer, M.Knapp, and B.Rupp (2002).
Structural basis for abrogated binding between staphylococcal enterotoxin A superantigen vaccine and MHC-IIalpha.
  Protein Sci, 11, 642-651.
PDB code: 1dyq
11972634 H.Pettersson, and G.Forsberg (2002).
Staphylococcal enterotoxin H contrasts closely related enterotoxins in species reactivity.
  Immunology, 106, 71-79.  
11895985 J.W.Shupp, M.Jett, and C.H.Pontzer (2002).
Identification of a transcytosis epitope on staphylococcal enterotoxins.
  Infect Immun, 70, 2178-2186.  
11934896 Y.I.Chi, I.Sadler, L.M.Jablonski, S.D.Callantine, C.F.Deobald, C.V.Stauffacher, and G.A.Bohach (2002).
Zinc-mediated dimerization and its effect on activity and conformation of staphylococcal enterotoxin type C.
  J Biol Chem, 277, 22839-22846.
PDB code: 1ck1
11290341 C.T.Morita, H.Li, J.G.Lamphear, R.R.Rich, J.D.Fraser, R.A.Mariuzza, and H.K.Lee (2001).
Superantigen recognition by gammadelta T cells: SEA recognition site for human Vgamma2 T cell receptors.
  Immunity, 14, 331-344.  
11307922 D.L.Hu, K.Omoe, M.H.Saleh, K.Ono, S.Sugii, A.Nakane, and K.Shinagawa (2001).
Analysis of the epitopes on staphylococcal enterotoxin A responsible for emetic activity.
  J Vet Med Sci, 63, 237-241.  
11437414 G.Forsberg, L.Ohlsson, T.Brodin, P.Björk, P.A.Lando, D.Shaw, P.L.Stern, and M.Dohlsten (2001).
Therapy of human non-small-cell lung carcinoma using antibody targeting of a modified superantigen.
  Br J Cancer, 85, 129-136.  
11544350 J.K.McCormick, J.M.Yarwood, and P.M.Schlievert (2001).
Toxic shock syndrome and bacterial superantigens: an update.
  Annu Rev Microbiol, 55, 77.  
11432818 K.Petersson, M.Håkansson, H.Nilsson, G.Forsberg, L.A.Svensson, A.Liljas, and B.Walse (2001).
Crystal structure of a superantigen bound to MHC class II displays zinc and peptide dependence.
  EMBO J, 20, 3306-3312.
PDB code: 1hxy
11369867 M.Baker, D.M.Gutman, A.C.Papageorgiou, C.M.Collins, and K.R.Acharya (2001).
Structural features of a zinc binding site in the superantigen strepococcal pyrogenic exotoxin A (SpeA1): implications for MHC class II recognition.
  Protein Sci, 10, 1268-1273.
PDB code: 1ha5
11119525 P.M.Orwin, D.Y.Leung, H.L.Donahue, R.P.Novick, and P.M.Schlievert (2001).
Biochemical and biological properties of Staphylococcal enterotoxin K.
  Infect Immun, 69, 360-366.  
10920396 A.C.Papageorgiou, and K.R.Acharya (2000).
Microbial superantigens: from structure to function.
  Trends Microbiol, 8, 369-375.  
10636860 A.Cavallin, H.Arozenius, K.Kristensson, P.Antonsson, D.E.Otzen, P.Björk, and G.Forsberg (2000).
The spectral and thermodynamic properties of staphylococcal enterotoxin A, E, and variants suggest that structural modifications are important to control their function.
  J Biol Chem, 275, 1665-1672.  
  11045630 C.A.Earhart, G.M.Vath, M.Roggiani, P.M.Schlievert, and D.H.Ohlendorf (2000).
Structure of streptococcal pyrogenic exotoxin A reveals a novel metal cluster.
  Protein Sci, 9, 1847-1851.
PDB codes: 1fnu 1fnv 1fnw
10873861 F.A.Saul, P.Rovira, G.Boulot, E.J.Damme, W.J.Peumans, P.Truffa-Bachi, and G.A.Bentley (2000).
Crystal structure of Urtica dioica agglutinin, a superantigen presented by MHC molecules of class I and class II.
  Structure, 8, 593-603.
PDB codes: 1eis 1en2 1enm
10627489 M.M.Dinges, P.M.Orwin, and P.M.Schlievert (2000).
Exotoxins of Staphylococcus aureus.
  Clin Microbiol Rev, 13, 16.  
9878045 A.C.Papageorgiou, C.M.Collins, D.M.Gutman, J.B.Kline, S.M.O'Brien, H.S.Tranter, and K.R.Acharya (1999).
Structural basis for the recognition of superantigen streptococcal pyrogenic exotoxin A (SpeA1) by MHC class II molecules and T-cell receptors.
  EMBO J, 18, 9.
PDB code: 1b1z
10459578 D.L.Hu, K.Omoe, A.Nakane, S.Sugii, K.Ono, S.Sasaki, and K.Shinagawa (1999).
Studies on the functional site on staphylococcal enterotoxin A responsible for production of murine gamma interferon.
  FEMS Immunol Med Microbiol, 25, 237-244.  
10358765 H.Li, A.Llera, E.L.Malchiodi, and R.A.Mariuzza (1999).
The structural basis of T cell activation by superantigens.
  Annu Rev Immunol, 17, 435-466.  
10399079 P.M.Lavoie, J.Thibodeau, F.Erard, and R.P.Sékaly (1999).
Understanding the mechanism of action of bacterial superantigens from a decade of research.
  Immunol Rev, 168, 257-269.  
  10194458 S.Ladhani, C.L.Joannou, D.P.Lochrie, R.W.Evans, and S.M.Poston (1999).
Clinical, microbial, and biochemical aspects of the exfoliative toxins causing staphylococcal scalded-skin syndrome.
  Clin Microbiol Rev, 12, 224-242.  
  10614742 S.Macphail (1999).
Superantigens: mechanisms by which they may induce, exacerbate and control autoimmune diseases.
  Int Rev Immunol, 18, 141-180.  
9874566 T.Proft, S.L.Moffatt, C.J.Berkahn, and J.D.Fraser (1999).
Identification and characterization of novel superantigens from Streptococcus pyogenes.
  J Exp Med, 189, 89.  
  10085033 W.Mahana (1999).
Mapping of staphylococcal enterotoxin A functional binding sites and presentation by monoclonal antibodies and fusion proteins.
  Infect Immun, 67, 1894-1900.  
10406939 Y.Ito, G.Seprényi, J.Abe, and T.Kohsaka (1999).
Analysis of functional regions of YPM, a superantigen derived from gram-negative bacteria.
  Eur J Biochem, 263, 326-337.  
9585531 C.A.Earhart, D.T.Mitchell, D.L.Murray, D.M.Pinheiro, M.Matsumura, P.M.Schlievert, and D.H.Ohlendorf (1998).
Structures of five mutants of toxic shock syndrome toxin-1 with reduced biological activity.
  Biochemistry, 37, 7194-7202.
PDB codes: 1aw7 1ts2 1ts3 1ts4 1ts5
9795898 D.L.Hu, A.Imai, K.Ono, S.Sasaki, A.Nakane, S.Sugii, and K.Shinagawa (1998).
Epitope analysis of staphylococcal enterotoxin A using different synthetic peptides.
  J Vet Med Sci, 60, 993-996.  
9881971 H.Li, A.Llera, D.Tsuchiya, L.Leder, X.Ysern, P.M.Schlievert, K.Karjalainen, and R.A.Mariuzza (1998).
Three-dimensional structure of the complex between a T cell receptor beta chain and the superantigen staphylococcal enterotoxin B.
  Immunity, 9, 807-816.
PDB code: 1sbb
9881589 I.A.Desouza, and G.Ribeiro-DaSilva (1998).
Neutrophil migration induced by staphylococcal enterotoxin type A in mice: a pharmacological analysis.
  Eur J Pharmacol, 363, 189-195.  
  9746612 J.Yamaoka, E.Nakamura, Y.Takeda, S.Imamura, and N.Minato (1998).
Mutational analysis of superantigen activity responsible for the induction of skin erythema by streptococcal pyrogenic exotoxin C.
  Infect Immun, 66, 5020-5026.  
10837621 M.Dohlsten, T.Kalland, P.Gunnarsson, P.Antonsson, A.Molander, J.Olsson, R.d'Argy, L.Ohlsson, M.Soegaard, R.Persson, and T.N.Brodin (1998).
Man-made superantigens: Tumor-selective agents for T-cell-based therapy.
  Adv Drug Deliv Rev, 31, 131-142.  
10066470 M.Kotb (1998).
Superantigens of gram-positive bacteria: structure-function analyses and their implications for biological activity.
  Curr Opin Microbiol, 1, 56-65.  
  9632603 S.H.Munson, M.T.Tremaine, M.J.Betley, and R.A.Welch (1998).
Identification and characterization of staphylococcal enterotoxin types G and I from Staphylococcus aureus.
  Infect Immun, 66, 3337-3348.  
9835033 S.Zhang, J.J.Iandolo, and G.C.Stewart (1998).
The enterotoxin D plasmid of Staphylococcus aureus encodes a second enterotoxin determinant (sej).
  FEMS Microbiol Lett, 168, 227-233.  
9309216 A.C.Papageorgiou, and K.R.Acharya (1997).
Superantigens as immunomodulators: recent structural insights.
  Structure, 5, 991-996.  
9218781 A.D.Cameron, B.Olin, M.Ridderström, B.Mannervik, and T.A.Jones (1997).
Crystal structure of human glyoxalase I--evidence for gene duplication and 3D domain swapping.
  EMBO J, 16, 3386-3395.
PDB code: 1fro
  9393804 A.Rosendahl, J.Hansson, P.Antonsson, R.P.Sékaly, T.Kalland, and M.Dohlsten (1997).
A mutation of F47 to A in staphylococcus enterotoxin A activates the T-cell receptor Vbeta repertoire in vivo.
  Infect Immun, 65, 5118-5124.  
9253413 A.Roussel, B.F.Anderson, H.M.Baker, J.D.Fraser, and E.N.Baker (1997).
Crystal structure of the streptococcal superantigen SPE-C: dimerization and zinc binding suggest a novel mode of interaction with MHC class II molecules.
  Nat Struct Biol, 4, 635-643.
PDB code: 1an8
9188741 A.V.Efimov (1997).
Structural trees for protein superfamilies.
  Proteins, 28, 241-260.  
  9317026 B.C.Cole, A.D.Sawitzke, E.A.Ahmed, C.L.Atkin, and C.S.David (1997).
Allelic polymorphisms at the H-2A and HLA-DQ loci influence the response of murine lymphocytes to the Mycoplasma arthritidis superantigen MAM.
  Infect Immun, 65, 4190-4198.  
  9169724 C.Bernatchez, R.Al-Daccak, P.E.Mayer, K.Mehindate, L.Rink, S.Mecheri, and W.Mourad (1997).
Functional analysis of Mycoplasma arthritidis-derived mitogen interactions with class II molecules.
  Infect Immun, 65, 2000-2005.  
9048539 G.M.Vath, C.A.Earhart, J.V.Rago, M.H.Kim, G.A.Bohach, P.M.Schlievert, and D.H.Ohlendorf (1997).
The structure of the superantigen exfoliative toxin A suggests a novel regulation as a serine protease.
  Biochemistry, 36, 1559-1566.
PDB code: 1exf
  9194182 G.S.Prasad, R.Radhakrishnan, D.T.Mitchell, C.A.Earhart, M.M.Dinges, W.J.Cook, P.M.Schlievert, and D.H.Ohlendorf (1997).
Refined structures of three crystal forms of toxic shock syndrome toxin-1 and of a tetramutant with reduced activity.
  Protein Sci, 6, 1220-1227.
PDB codes: 2tss 3tss 4tss 5tss
9122222 J.Hansson, L.Ohlsson, R.Persson, G.Andersson, N.G.Ilbäck, M.J.Litton, T.Kalland, and M.Dohlsten (1997).
Genetically engineered superantigens as tolerable antitumor agents.
  Proc Natl Acad Sci U S A, 94, 2489-2494.  
  9317006 J.R.Deringer, R.J.Ely, S.R.Monday, C.V.Stauffacher, and G.A.Bohach (1997).
Vbeta-dependent stimulation of bovine and human T cells by host-specific staphylococcal enterotoxins.
  Infect Immun, 65, 4048-4054.  
  9199461 M.Roggiani, J.A.Stoehr, B.A.Leonard, and P.M.Schlievert (1997).
Analysis of toxicity of streptococcal pyrogenic exotoxin A mutants.
  Infect Immun, 65, 2868-2875.  
9236189 P.L.Li, R.E.Tiedemann, S.L.Moffat, and J.D.Fraser (1997).
The superantigen streptococcal pyrogenic exotoxin C (SPE-C) exhibits a novel mode of action.
  J Exp Med, 186, 375-383.  
9022003 Y.Bravo de Alba, P.N.Marche, P.A.Cazenave, I.Cloutier, R.P.Sekaly, and J.Thibodeau (1997).
V alpha domain modulates the multiple topologies of mouse T cell receptor V beta20/staphylococcal enterotoxins A and E complexes.
  Eur J Immunol, 27, 92-99.  
  8557369 D.L.Murray, C.A.Earhart, D.T.Mitchell, D.H.Ohlendorf, R.P.Novick, and P.M.Schlievert (1996).
Localization of biologically important regions on toxic shock syndrome toxin 1.
  Infect Immun, 64, 371-374.  
8814249 K.Mehindate,, F.Damdoumi, and W.Mourad (1996).
Synergistic effect between CD40 and class II signals overcome the requirement for class II dimerization in superantigen-induced cytokine gene expression.
  Eur J Immunol, 26, 2075-2080.  
8879218 L.Liao, A.Marinescu, A.Molano, C.Ciurli, R.P.Sekaly, J.D.Fraser, A.Popowicz, and D.N.Posnett (1996).
TCR binding differs for a bacterial superantigen (SEE) and a viral superantigen (Mtv-9).
  J Exp Med, 184, 1471-1482.  
  8641796 M.Hoffman, M.Tremaine, J.Mansfield, and M.Betley (1996).
Biochemical and mutational analysis of the histidine residues of staphylococcal enterotoxin A.
  Infect Immun, 64, 885-890.  
9373308 M.Søgaard, J.Hansson, M.J.Litton, L.Ohlsson, A.Rosendahl, P.A.Lando, P.Antonsson, T.Kalland, and M.Dohlsten (1996).
Antibody-targeted superantigens in cancer immunotherapy.
  Immunotechnology, 2, 151-162.  
8943278 M.Sundström, D.Hallén, A.Svensson, E.Schad, M.Dohlsten, and L.Abrahmsén (1996).
The Co-crystal structure of staphylococcal enterotoxin type A with Zn2+ at 2.7 A resolution. Implications for major histocompatibility complex class II binding.
  J Biol Chem, 271, 32212-32216.
PDB code: 1sxt
  9003758 M.Sundström, L.Abrahmsén, P.Antonsson, K.Mehindate, W.Mourad, and M.Dohlsten (1996).
The crystal structure of staphylococcal enterotoxin type D reveals Zn2+-mediated homodimerization.
  EMBO J, 15, 6832-6840.  
8966664 P.Antonsson, J.Hansson, T.Kalland, P.A.Lando, L.Ohlsson, E.Schad, A.Svensson, and M.Dohlsten (1996).
Genetically engineered superantigens in experimental tumor therapy.
  Springer Semin Immunopathol, 17, 397-410.  
7595227 K.Mehindate, J.Thibodeau, M.Dohlsten, T.Kalland, R.P.Sékaly, and W.Mourad (1995).
Cross-linking of major histocompatibility complex class II molecules by staphylococcal enterotoxin A superantigen is a requirement for inflammatory cytokine gene expression.
  J Exp Med, 182, 1573-1577.  
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.