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PDBsum entry 1bqb
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.24.29
- aureolysin.
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Reaction:
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Cleavage of insulin B chain with specificity similar to that of thermolysin, preferring hydrophobic P1' residues. Activates the glutamyl endopeptidase (EC 3.4.21.19) of Staphylococcus aureus.
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Cofactor:
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Ca(2+); Zn(2+)
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DOI no:
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Structure
6:1185-1193
(1998)
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PubMed id:
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Amino-acid sequence and three-dimensional structure of the Staphylococcus aureus metalloproteinase at 1.72 A resolution.
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A.Banbula,
J.Potempa,
J.Travis,
C.Fernandez-Catalán,
K.Mann,
R.Huber,
W.Bode,
F.Medrano.
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ABSTRACT
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BACKGROUND: Aureolysin is an extracellular zinc-dependent metalloproteinase from
the pathogenic bacterium Staphylococcus aureus. This enzyme exhibits in vitro
activity against several molecules of biological significance for the host,
indicating that it is involved in the pathology of staphylococcal diseases.
RESULTS: Here we report the amino-acid sequence and inhibitor-free X-ray crystal
structure of aureolysin, a member of the thermolysin family of zinc-dependent
metalloproteinases. This enzyme, which binds one zinc and three calcium ions,
comprises a single chain of 301 amino acids that consists of a beta-strand-rich
upper domain and an alpha-helix-rich lower domain. CONCLUSIONS: The overall
structure of aureolysin is very similar to that of the other three members of
this family whose structures are known - thermolysin (TLN) from Bacillus
thermoproteolyticus, neutral protease (NP) from Bacillus cereus and elastase
(PAE) from Pseudomonas aeruginosa. But an important difference has been
encountered: in contrast to what has been observed in the other three members of
this family (TLN, NP and PAE), inhibitor-free aureolysin displays a 'closed'
active site cleft conformation. This new structure therefore raises questions
about the universality of the hinge-bending motion model for the neutral
metalloproteinases.
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Selected figure(s)
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Figure 5.
Figure 5. Superposition of (a) the residues from the
N-terminal subdomain that contribute to the `upper' lip of the
active-site cleft and (b) the calcium-binding sites of
aureolysin on thermolysin. The spheres represent the calcium
ions. Aureolysin is shown in black and thermolysin in grey. This
figure was prepared with the program SETOR [34].
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1998,
6,
1185-1193)
copyright 1998.
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Figure was
selected
by an automated process.
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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.Ruf,
M.Stihle,
J.Benz,
M.Schmidt,
and
H.Sobek
(2013).
Structure of Gentlyase, the neutral metalloprotease of Paenibacillus polymyxa.
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Acta Crystallogr D Biol Crystallogr,
69,
24-31.
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PDB codes:
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I.V.Demidyuk,
T.Y.Gromova,
K.M.Polyakov,
W.R.Melik-Adamyan,
I.P.Kuranova,
and
S.V.Kostrov
(2010).
Crystal structure of the protealysin precursor: insights into propeptide function.
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J Biol Chem,
285,
2003-2013.
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PDB code:
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N.Beaufort,
P.Seweryn,
S.de Bentzmann,
A.Tang,
J.Kellermann,
N.Grebenchtchikov,
M.Schmitt,
C.P.Sommerhoff,
D.Pidard,
and
V.Magdolen
(2010).
Activation of human pro-urokinase by unrelated proteases secreted by Pseudomonas aeruginosa.
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Biochem J,
428,
473-482.
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B.B.Xie,
F.Bian,
X.L.Chen,
H.L.He,
J.Guo,
X.Gao,
Y.X.Zeng,
B.Chen,
B.C.Zhou,
and
Y.Z.Zhang
(2009).
Cold adaptation of zinc metalloproteases in the thermolysin family from deep sea and arctic sea ice bacteria revealed by catalytic and structural properties and molecular dynamics: new insights into relationship between conformational flexibility and hydrogen bonding.
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J Biol Chem,
284,
9257-9269.
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O.A.Adekoya,
and
I.Sylte
(2009).
The thermolysin family (m4) of enzymes: therapeutic and biotechnological potential.
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Chem Biol Drug Des,
73,
7.
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A.J.Sabat,
B.Wladyka,
K.Kosowska-Shick,
H.Grundmann,
J.M.van Dijl,
J.Kowal,
P.C.Appelbaum,
A.Dubin,
and
W.Hryniewicz
(2008).
Polymorphism, genetic exchange and intragenic recombination of the aureolysin gene among Staphylococcus aureus strains.
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BMC Microbiol,
8,
129.
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A.P.Bitar,
M.Cao,
and
H.Marquis
(2008).
The metalloprotease of Listeria monocytogenes is activated by intramolecular autocatalysis.
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J Bacteriol,
190,
107-111.
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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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F.C.Tenover,
L.K.McDougal,
R.V.Goering,
G.Killgore,
S.J.Projan,
J.B.Patel,
and
P.M.Dunman
(2006).
Characterization of a strain of community-associated methicillin-resistant Staphylococcus aureus widely disseminated in the United States.
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J Clin Microbiol,
44,
108-118.
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M.Kawalec,
J.Potempa,
J.L.Moon,
J.Travis,
and
B.E.Murray
(2005).
Molecular diversity of a putative virulence factor: purification and characterization of isoforms of an extracellular serine glutamyl endopeptidase of Enterococcus faecalis with different enzymatic activities.
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J Bacteriol,
187,
266-275.
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A.de Kreij,
B.van den Burg,
G.Venema,
G.Vriend,
V.G.Eijsink,
and
J.E.Nielsen
(2002).
The effects of modifying the surface charge on the catalytic activity of a thermolysin-like protease.
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J Biol Chem,
277,
15432-15438.
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C.T.Supuran,
A.Scozzafava,
and
B.W.Clare
(2002).
Bacterial protease inhibitors.
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Med Res Rev,
22,
329-372.
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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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A.de Kreij,
B.van den Burg,
O.R.Veltman,
G.Vriend,
G.Venema,
and
V.G.Eijsink
(2001).
The effect of changing the hydrophobic S1' subsite of thermolysin-like proteases on substrate specificity.
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Eur J Biochem,
268,
4985-4991.
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G.Dubin,
D.Chmiel,
P.Mak,
M.Rakwalska,
M.Rzychon,
and
A.Dubin
(2001).
Molecular cloning and biochemical characterisation of proteases from Staphylococcus epidermidis.
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Biol Chem,
382,
1575-1582.
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T.Hori,
T.Kumasaka,
M.Yamamoto,
N.Nonaka,
N.Tanaka,
Y.Hashimoto,
U.Ueki,
and
K.Takio
(2001).
Structure of a new 'aspzincin' metalloendopeptidase from Grifola frondosa: implications for the catalytic mechanism and substrate specificity based on several different crystal forms.
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Acta Crystallogr D Biol Crystallogr,
57,
361-368.
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PDB codes:
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A.Sabat,
K.Kosowska,
K.Poulsen,
A.Kasprowicz,
A.Sekowska,
B.van Den Burg,
J.Travis,
and
J.Potempa
(2000).
Two allelic forms of the aureolysin gene (aur) within Staphylococcus aureus.
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Infect Immun,
68,
973-976.
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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
codes are
shown on the right.
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Links
