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PDBsum entry 1exf
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Complex (toxin/peptide)
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PDB id
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1exf
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Contents |
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* Residue conservation analysis
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DOI no:
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Biochemistry
36:1559-1566
(1997)
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PubMed id:
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The structure of the superantigen exfoliative toxin A suggests a novel regulation as a serine protease.
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G.M.Vath,
C.A.Earhart,
J.V.Rago,
M.H.Kim,
G.A.Bohach,
P.M.Schlievert,
D.H.Ohlendorf.
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ABSTRACT
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Exfoliative toxin A (ETA) causes staphylococcal scalded skin syndrome which is
characterized by a specific intraepidermal separation of layers of the skin. The
mechanism by which ETA causes skin separation is unknown although protease or
superantigen activity has been implicated. The X-ray crystal structure of ETA
has been solved in two crystal forms to 2.1 and 2.3 A resolution and R-factors
of 17% and 19%, respectively. The structures indicate that ETA belongs to the
chymotrypsin-like family of serine proteases and cleaves substrates after acidic
residues. The conformation of a loop adjacent to the catalytic site is suggested
to be key in regulating the proteolytic activity of ETA through controlling
whether the main chain carbonyl group of Pro192 occupies the oxyanion hole. A
unique amino-terminal domain containing a 15-residue amphipathic alpha helix may
also be involved in protease activation through binding a specific receptor.
Substitution of the active site serine residue with cysteine abolishes the
ability of ETA to produce the characteristic separation of epidermal layers but
not its ability to induce T cell proliferation.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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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.
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J Phys Chem B,
114,
16125-16130.
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K.Iyori,
J.Hisatsune,
T.Kawakami,
S.Shibata,
N.Murayama,
K.Ide,
M.Nagata,
T.Fukata,
T.Iwasaki,
K.Oshima,
M.Hattori,
M.Sugai,
and
K.Nishifuji
(2010).
Identification of a novel Staphylococcus pseudintermedius exfoliative toxin gene and its prevalence in isolates from canines with pyoderma and healthy dogs.
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FEMS Microbiol Lett,
312,
169-175.
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M.Amagai
(2010).
Autoimmune and infectious skin diseases that target desmogleins.
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Proc Jpn Acad Ser B Phys Biol Sci,
86,
524-537.
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T.Funakoshi,
and
A.S.Payne
(2010).
Cleavage isn't everything: potential novel mechanisms of exfoliative toxin-mediated blistering.
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Am J Pathol,
177,
2682-2684.
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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.
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Pediatr Crit Care Med,
11,
e20-e23.
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Z.Chen,
L.A.Pelc,
and
E.Di Cera
(2010).
Crystal structure of prethrombin-1.
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Proc Natl Acad Sci U S A,
107,
19278-19283.
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PDB code:
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N.N.Nickerson,
L.Prasad,
L.Jacob,
L.T.Delbaere,
and
M.J.McGavin
(2007).
Activation of the SspA serine protease zymogen of Staphylococcus aureus proceeds through unique variations of a trypsinogen-like mechanism and is dependent on both autocatalytic and metalloprotease-specific processing.
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J Biol Chem,
282,
34129-34138.
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M.Amagai
(2006).
[Desmoglein, the target molecule in autoimmunity and infection]
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Nihon Rinsho Meneki Gakkai Kaishi,
29,
325-333.
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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.
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J Biol Chem,
281,
24873-24888.
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PDB codes:
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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.
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J Biol Chem,
280,
9160-9169.
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PDB code:
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J.R.Birtley,
S.R.Knox,
A.M.Jaulent,
P.Brick,
R.J.Leatherbarrow,
and
S.Curry
(2005).
Crystal structure of foot-and-mouth disease virus 3C protease. New insights into catalytic mechanism and cleavage specificity.
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J Biol Chem,
280,
11520-11527.
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PDB code:
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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.
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J Biol Chem,
279,
29485-29492.
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A.S.Payne,
Y.Hanakawa,
M.Amagai,
and
J.R.Stanley
(2004).
Desmosomes and disease: pemphigus and bullous impetigo.
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Curr Opin Cell Biol,
16,
536-543.
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L.Prasad,
Y.Leduc,
K.Hayakawa,
and
L.T.Delbaere
(2004).
The structure of a universally employed enzyme: V8 protease from Staphylococcus aureus.
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Acta Crystallogr D Biol Crystallogr,
60,
256-259.
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PDB codes:
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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.
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J Biol Chem,
279,
5268-5277.
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S.Ladhani
(2003).
Understanding the mechanism of action of the exfoliative toxins of Staphylococcus aureus.
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FEMS Immunol Med Microbiol,
39,
181-189.
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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.
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J Invest Dermatol,
121,
383-389.
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D.T.Jones,
and
M.B.Swindells
(2002).
Getting the most from PSI-BLAST.
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Trends Biochem Sci,
27,
161-164.
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G.Dubin
(2002).
Extracellular proteases of Staphylococcus spp.
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Biol Chem,
383,
1075-1086.
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M.Amagai,
T.Yamaguchi,
Y.Hanakawa,
K.Nishifuji,
M.Sugai,
and
J.R.Stanley
(2002).
Staphylococcal exfoliative toxin B specifically cleaves desmoglein 1.
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J Invest Dermatol,
118,
845-850.
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S.Ladhani,
J.Cameron,
D.S.Chapple,
R.C.Garratt,
C.L.Joannou,
and
R.W.Evans
(2002).
A novel method for rapid production and purification of exfoliative toxin A of Staphylococcus aureus.
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FEMS Microbiol Lett,
212,
35-39.
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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.
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Infect Immun,
70,
5835-5845.
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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.
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J Clin Invest,
110,
53-60.
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D.Kumaran,
S.Eswaramoorthy,
W.Furey,
M.Sax,
and
S.Swaminathan
(2001).
Structure of staphylococcal enterotoxin C2 at various pH levels.
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Acta Crystallogr D Biol Crystallogr,
57,
1270-1275.
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PDB codes:
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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.
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Infect Immun,
69,
5193-5197.
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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.
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J Clin Microbiol,
39,
2050-2054.
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S.Ladhani
(2001).
Recent developments in staphylococcal scalded skin syndrome.
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Clin Microbiol Infect,
7,
301-307.
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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.
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Infect Immun,
69,
7760-7771.
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W.H.Boehncke,
K.Hardt-Weinelt,
H.Nilsson,
M.Wolter,
M.Dohlsten,
F.R.Ochsendorf,
R.Kaufmann,
and
P.Antonsson
(2001).
Antagonistic effects of the staphylococcal enterotoxin a mutant, SEA(F47A/D227A), on psoriasis in the SCID-hu xenogeneic transplantation model.
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J Invest Dermatol,
116,
596-601.
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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.
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Protein Sci,
9,
610-618.
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PDB codes:
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J.Ninomiya,
Y.Ito,
and
I.Takiuchi
(2000).
Purification of protease from a mixture of exfoliative toxin and newborn-mouse epidermis.
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Infect Immun,
68,
5044-5049.
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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.
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Infect Immun,
68,
2366-2368.
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L.R.Plano,
D.M.Gutman,
M.Woischnik,
and
C.M.Collins
(2000).
Recombinant Staphylococcus aureus exfoliative toxins are not bacterial superantigens.
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Infect Immun,
68,
3048-3052.
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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.
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Mol Microbiol,
38,
694-705.
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A.M.Farrell
(1999).
Staphylococcal scalded-skin syndrome.
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Lancet,
354,
880-881.
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H.Czapinska,
and
J.Otlewski
(1999).
Structural and energetic determinants of the S1-site specificity in serine proteases.
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Eur J Biochem,
260,
571-595.
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H.Li,
A.Llera,
E.L.Malchiodi,
and
R.A.Mariuzza
(1999).
The structural basis of T cell activation by superantigens.
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Annu Rev Immunol,
17,
435-466.
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K.M.Acland,
A.Darvay,
C.Griffin,
S.A.Aali,
and
R.Russell-Jones
(1999).
Staphylococcal scalded skin syndrome in an adult associated with methicillin-resistant Staphylococcus aureus.
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Br J Dermatol,
140,
518-520.
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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.
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Immunol Rev,
168,
257-269.
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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.
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Clin Microbiol Rev,
12,
224-242.
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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.
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Immunity,
9,
807-816.
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PDB code:
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H.Li,
A.Llera,
and
R.A.Mariuzza
(1998).
Structure-function studies of T-cell receptor-superantigen interactions.
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Immunol Rev,
163,
177-186.
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M.Kotb
(1998).
Superantigens of gram-positive bacteria: structure-function analyses and their implications for biological activity.
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Curr Opin Microbiol,
1,
56-65.
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S.Ladhani,
and
R.W.Evans
(1998).
Staphylococcal scalded skin syndrome.
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Arch Dis Child,
78,
85-88.
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A.Marchler-Bauer,
and
S.H.Bryant
(1997).
A measure of success in fold recognition.
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Trends Biochem Sci,
22,
236-240.
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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.
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Links
