PDBsum entry 1agj

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protein Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
242 a.a. *
Waters ×417
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Epidermolytic toxin a from staphylococcus aureus
Structure: Epidermolytic toxin a. Chain: a, b. Ec: 3.4.21.-
Source: Staphylococcus aureus. Organism_taxid: 1280. Strain: ibs-sa417
1.70Å     R-factor:   0.184     R-free:   0.235
Authors: J.Cavarelli
Key ref:
J.Cavarelli et al. (1997). The structure of Staphylococcus aureus epidermolytic toxin A, an atypic serine protease, at 1.7 A resolution. Structure, 5, 813-824. PubMed id: 9261066 DOI: 10.1016/S0969-2126(97)00235-9
25-Mar-97     Release date:   26-Sep-97    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P09331  (ETA_STAAU) -  Exfoliative toxin A
280 a.a.
242 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1016/S0969-2126(97)00235-9 Structure 5:813-824 (1997)
PubMed id: 9261066  
The structure of Staphylococcus aureus epidermolytic toxin A, an atypic serine protease, at 1.7 A resolution.
J.Cavarelli, G.Prévost, W.Bourguet, L.Moulinier, B.Chevrier, B.Delagoutte, A.Bilwes, L.Mourey, S.Rifai, Y.Piémont, D.Moras.
BACKGROUND: Staphylococcal epidermolytic toxins A and B (ETA and ETB) are responsible for the staphylococcal scalded skin syndrome of newborn and young infants; this condition can appear just a few hours after birth. These toxins cause the disorganization and disruption of the region between the stratum spinosum and the stratum granulosum--two of the three cellular layers constituting the epidermis. The physiological substrate of ETA is not known and, consequently, its mode of action in vivo remains an unanswered question. Determination of the structure of ETA and its comparison with other serine proteases may reveal insights into ETA's catalytic mechanism. RESULTS: The crystal structure of staphylococcal ETA has been determined by multiple isomorphous replacement and refined at 1.7 A resolution with a crystallographic R factor of 0.184. The structure of ETA reveals it to be a new and unique member of the trypsin-like serine protease family. In contrast to other serine protease folds, ETA can be characterized by ETA-specific surface loops, a lack of cysteine bridges, an oxyanion hole which is not preformed, an S1 specific pocket designed for a negatively charged amino acid and an ETA-specific specific N-terminal helix which is shown to be crucial for substrate hydrolysis. CONCLUSIONS: Despite very low sequence homology between ETA and other trypsin-like serine proteases, the ETA crystal structure, together with biochemical data and site-directed mutagenesis studies, strongly confirms the classification of ETA in the Glu-endopeptidase family. Direct links can be made between the protease architecture of ETA and its biological activity.
  Selected figure(s)  
Figure 2.
Figure 2. Schematic drawing of the structure of ETA. The two domains, built around a six-stranded antiparallel b sheet characteristic of the trypsin-like serine protease fold, are shown in green for domain I and in red for domain II. The location of the catalytic tetrad, His72(57), Asp120(102), Ser195(195) and Ser211(214), is shown together with the amino acid residues which map the S1 specific pocket. The canonical surface loops [26] (loops A, B, C, D, 1, 2 and 3) are shown in blue. Numbering is only shown according to the mature sequence of ETA.
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 813-824) copyright 1997.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20809655 A.D.Vogt, A.Bah, and E.Di Cera (2010).
Evidence of the E*-E equilibrium from rapid kinetics of Na+ binding to activated protein C and factor Xa.
  J Phys Chem B, 114, 16125-16130.  
20467217 M.Amagai (2010).
Autoimmune and infectious skin diseases that target desmogleins.
  Proc Jpn Acad Ser B Phys Biol Sci, 86, 524-537.  
20216172 W.B.Norbury, J.J.Gallagher, D.N.Herndon, L.K.Branski, P.E.Oehring, and M.G.Jeschke (2010).
Neonate twin with staphylococcal scalded skin syndrome from a renal source.
  Pediatr Crit Care Med, 11, e20-e23.  
16757484 S.P.Bajaj, A.E.Schmidt, S.Agah, M.S.Bajaj, and K.Padmanabhan (2006).
High resolution structures of p-aminobenzamidine- and benzamidine-VIIa/soluble tissue factor: unpredicted conformation of the 192-193 peptide bond and mapping of Ca2+, Mg2+, Na+, and Zn2+ sites in factor VIIa.
  J Biol Chem, 281, 24873-24888.
PDB codes: 2a2q 2aer 2fir
15632123 A.G.Olivero, C.Eigenbrot, R.Goldsmith, K.Robarge, D.R.Artis, J.Flygare, T.Rawson, D.P.Sutherlin, S.Kadkhodayan, M.Beresini, L.O.Elliott, G.G.DeGuzman, D.W.Banner, M.Ultsch, U.Marzec, S.R.Hanson, C.Refino, S.Bunting, and D.Kirchhofer (2005).
A selective, slow binding inhibitor of factor VIIa binds to a nonstandard active site conformation and attenuates thrombus formation in vivo.
  J Biol Chem, 280, 9160-9169.
PDB code: 1ygc
15750064 O.Joubert, D.Keller, A.Pinck, H.Monteil, and G.Prévost (2005).
Sensitive and specific detection of staphylococcal epidermolysins A and B in broth cultures by flow cytometry-assisted multiplex immunoassay.
  J Clin Microbiol, 43, 1076-1080.  
16091916 Z.Kato, K.Tsubouchi, and N.Kondo (2005).
Molluscum contagiosum prevents progression of staphylococcal scalded skin syndrome.
  Eur J Pediatr, 164, 768-769.  
15090552 A.E.Schmidt, T.Ogawa, D.Gailani, and S.P.Bajaj (2004).
Structural role of Gly(193) in serine proteases: investigations of a G555E (GLY193 in chymotrypsin) mutant of blood coagulation factor XI.
  J Biol Chem, 279, 29485-29492.  
14747701 L.Prasad, Y.Leduc, K.Hayakawa, and L.T.Delbaere (2004).
The structure of a universally employed enzyme: V8 protease from Staphylococcus aureus.
  Acta Crystallogr D Biol Crystallogr, 60, 256-259.
PDB codes: 1qy6 2o8l
14630910 Y.Hanakawa, N.M.Schechter, C.Lin, K.Nishifuji, M.Amagai, and J.R.Stanley (2004).
Enzymatic and molecular characteristics of the efficiency and specificity of exfoliative toxin cleavage of desmoglein 1.
  J Biol Chem, 279, 5268-5277.  
12458220 D.Y.Kim, D.R.Kim, S.C.Ha, N.K.Lokanath, C.J.Lee, H.Y.Hwang, and K.K.Kim (2003).
Crystal structure of the protease domain of a heat-shock protein HtrA from Thermotoga maritima.
  J Biol Chem, 278, 6543-6551.
PDB code: 1l1j
14625102 S.Ladhani (2003).
Understanding the mechanism of action of the exfoliative toxins of Staphylococcus aureus.
  FEMS Immunol Med Microbiol, 39, 181-189.  
12880431 Y.Hanakawa, T.Selwood, D.Woo, C.Lin, N.M.Schechter, and J.R.Stanley (2003).
Calcium-dependent conformation of desmoglein 1 is required for its cleavage by exfoliative toxin.
  J Invest Dermatol, 121, 383-389.  
12437090 G.Dubin (2002).
Extracellular proteases of Staphylococcus spp.
  Biol Chem, 383, 1075-1086.  
12377789 J.Phan, A.Zdanov, A.G.Evdokimov, J.E.Tropea, H.K.Peters, R.B.Kapust, M.Li, A.Wlodawer, and D.S.Waugh (2002).
Structural basis for the substrate specificity of tobacco etch virus protease.
  J Biol Chem, 277, 50564-50572.
PDB codes: 1lvb 1lvm
12228315 T.Yamaguchi, K.Nishifuji, M.Sasaki, Y.Fudaba, M.Aepfelbacher, T.Takata, M.Ohara, H.Komatsuzawa, M.Amagai, and M.Sugai (2002).
Identification of the Staphylococcus aureus etd pathogenicity island which encodes a novel exfoliative toxin, ETD, and EDIN-B.
  Infect Immun, 70, 5835-5845.  
  12093888 Y.Hanakawa, N.M.Schechter, C.Lin, L.Garza, H.Li, T.Yamaguchi, Y.Fudaba, K.Nishifuji, M.Sugai, M.Amagai, and J.R.Stanley (2002).
Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome.
  J Clin Invest, 110, 53-60.  
11724844 A.Gravet, P.Couppié, O.Meunier, E.Clyti, B.Moreau, R.Pradinaud, H.Monteil, and G.Prévost (2001).
Staphylococcus aureus isolated in cases of impetigo produces both epidermolysin A or B and LukE-LukD in 78% of 131 retrospective and prospective cases.
  J Clin Microbiol, 39, 4349-4356.  
11447206 L.R.Plano, B.Adkins, M.Woischnik, R.Ewing, and C.M.Collins (2001).
Toxin levels in serum correlate with the development of staphylococcal scalded skin syndrome in a murine model.
  Infect Immun, 69, 5193-5197.  
11376033 S.Ladhani, S.Robbie, R.C.Garratt, D.S.Chapple, C.L.Joannou, and R.W.Evans (2001).
Development and evaluation of detection systems for staphylococcal exfoliative toxin A responsible for scalded-skin syndrome.
  J Clin Microbiol, 39, 2050-2054.  
11442563 S.Ladhani (2001).
Recent developments in staphylococcal scalded skin syndrome.
  Clin Microbiol Infect, 7, 301-307.  
11705958 T.Yamaguchi, T.Hayashi, H.Takami, M.Ohnishi, T.Murata, K.Nakayama, K.Asakawa, M.Ohara, H.Komatsuzawa, and M.Sugai (2001).
Complete nucleotide sequence of a Staphylococcus aureus exfoliative toxin B plasmid and identification of a novel ADP-ribosyltransferase, EDIN-C.
  Infect Immun, 69, 7760-7771.  
  10752623 A.C.Papageorgiou, L.R.Plano, C.M.Collins, and K.R.Acharya (2000).
Structural similarities and differences in Staphylococcus aureus exfoliative toxins A and B as revealed by their crystal structures.
  Protein Sci, 9, 610-618.
PDB codes: 1dt2 1dua 1due
10722646 J.V.Rago, G.M.Vath, T.J.Tripp, G.A.Bohach, D.H.Ohlendorf, and P.M.Schlievert (2000).
Staphylococcal exfoliative toxins cleave alpha- and beta-melanocyte-stimulating hormones.
  Infect Immun, 68, 2366-2368.  
10769013 L.R.Plano, D.M.Gutman, M.Woischnik, and C.M.Collins (2000).
Recombinant Staphylococcus aureus exfoliative toxins are not bacterial superantigens.
  Infect Immun, 68, 3048-3052.  
11115106 T.Yamaguchi, T.Hayashi, H.Takami, K.Nakasone, M.Ohnishi, K.Nakayama, S.Yamada, H.Komatsuzawa, and M.Sugai (2000).
Phage conversion of exfoliative toxin A production in Staphylococcus aureus.
  Mol Microbiol, 38, 694-705.  
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.  
  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.  
  9534685 S.Ladhani, and R.W.Evans (1998).
Staphylococcal scalded skin syndrome.
  Arch Dis Child, 78, 85-88.  
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.