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PDBsum entry 1ga6
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Hydrolase/hydrolase inhibitor
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PDB id
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1ga6
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.21.100
- sedolisin.
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Reaction:
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Hydrolysis of the B chain of insulin at 13-Glu-|-Ala-14, 15-Leu-|-Tyr-16 and 25-Phe-|-Tyr-26 and angiotensin I at 4-Tyr-|-Ile-5. A good synthetic substrate is Lys-Pro-Ile-Glu-Phe-|-Phe(NO(2))-Arg-Leu.
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DOI no:
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Nat Struct Biol
8:442-446
(2001)
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PubMed id:
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Carboxyl proteinase from Pseudomonas defines a novel family of subtilisin-like enzymes.
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A.Wlodawer,
M.Li,
Z.Dauter,
A.Gustchina,
K.Uchida,
H.Oyama,
B.M.Dunn,
K.Oda.
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ABSTRACT
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The crystal structure of a pepstatin-insensitive carboxyl proteinase from
Pseudomonas sp. 101 (PSCP) has been solved by single-wavelength anomalous
diffraction using the absorption peak of bromide anions. Structures of the
uninhibited enzyme and of complexes with an inhibitor that was either covalently
or noncovalently bound were refined at 1.0-1.4 A resolution. The structure of
PSCP comprises a single compact domain with a diameter of approximately 55 A,
consisting of a seven-stranded parallel beta-sheet flanked on both sides by a
number of helices. The fold of PSCP is a superset of the subtilisin fold, and
the covalently bound inhibitor is linked to the enzyme through a serine residue.
Thus, the structure of PSCP defines a novel family of serine-carboxyl
proteinases (defined as MEROPS S53) with a unique catalytic triad consisting of
Glu 80, Asp 84 and Ser 287.
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Selected figure(s)
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Figure 1.
Figure 1. Two views of the PSCP molecule. a, Stereo tracing
of the C  backbone
of PSCP (crystal D), with the side chains of the putative active
site residues (Ser 287, Glu 80, Asp 84) in ball-and-stick
representation. Every 20^th residue is labeled. Figure prepared
with Molscript34. b, Ribbon diagram showing protein in green,
active site residues in pink, Ca^2+ ion in yellow, and the
inhibitor found in crystals B and C in gold and blue,
respectively. Figure prepared using Ribbons35.
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Figure 3.
Figure 3. Chemical formulas and the electron density for the
inhibitors of PSCP. a, Chemical formula of iodotyrostatin. b,
Chemical formula of pseudo iodotyrostatin. c, Electron density
(2F[o] - F[c]) contoured at 0.8  for
the inhibitor found in crystal B, with the refined model
superimposed. All three common rotamers of Ser 287 can be
observed. d, Electron density (2F[o] -- F[c]) contoured at 0.85
for
the inhibitor covalently bound to Ser 287 in crystal C, with the
coordinates superimposed. The alternate orientation of the side
chain of Ser 287 is not marked.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2001,
8,
442-446)
copyright 2001.
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Figures were
selected
by the author.
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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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J.Vévodová,
M.Gamble,
G.Künze,
A.Ariza,
E.Dodson,
D.D.Jones,
and
K.S.Wilson
(2010).
Crystal structure of an intracellular subtilisin reveals novel structural features unique to this subtilisin family.
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Structure,
18,
744-755.
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PDB codes:
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M.E.Sanz,
J.C.López,
and
J.L.Alonso
(2010).
Six conformers of neutral aspartic acid identified in the gas phase.
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Phys Chem Chem Phys,
12,
3573-3578.
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A.Pal,
R.Kraetzner,
T.Gruene,
M.Grapp,
K.Schreiber,
M.Grønborg,
H.Urlaub,
S.Becker,
A.R.Asif,
J.Gärtner,
G.M.Sheldrick,
and
R.Steinfeld
(2009).
Structure of Tripeptidyl-peptidase I Provides Insight into the Molecular Basis of Late Infantile Neuronal Ceroid Lipofuscinosis.
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J Biol Chem,
284,
3976-3984.
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PDB code:
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J.Guhaniyogi,
I.Sohar,
K.Das,
A.M.Stock,
and
P.Lobel
(2009).
Crystal Structure and Autoactivation Pathway of the Precursor Form of Human Tripeptidyl-peptidase 1, the Enzyme Deficient in Late Infantile Ceroid Lipofuscinosis.
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J Biol Chem,
284,
3985-3997.
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PDB code:
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W.Nishii,
K.Kubota,
and
K.Takahashi
(2009).
The P1 and P1' residue specificities of physarolisin I, a serine-carboxyl peptidase from the true slime mold Physarum polycephalum.
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Biosci Biotechnol Biochem,
73,
1168-1171.
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O.D.Ekici,
M.Paetzel,
and
R.E.Dalbey
(2008).
Unconventional serine proteases: variations on the catalytic Ser/His/Asp triad configuration.
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Protein Sci,
17,
2023-2037.
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M.V.Shapovalov,
and
R.L.Dunbrack
(2007).
Statistical and conformational analysis of the electron density of protein side chains.
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Proteins,
66,
279-303.
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Q.Xu,
H.B.Guo,
A.Wlodawer,
T.Nakayama,
and
H.Guo
(2007).
The QM/MM molecular dynamics and free energy simulations of the acylation reaction catalyzed by the serine-carboxyl peptidase kumamolisin-As.
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Biochemistry,
46,
3784-3792.
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R.J.Siezen,
B.Renckens,
and
J.Boekhorst
(2007).
Evolution of prokaryotic subtilases: genome-wide analysis reveals novel subfamilies with different catalytic residues.
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Proteins,
67,
681-694.
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A.Okubo,
M.Li,
M.Ashida,
H.Oyama,
A.Gustchina,
K.Oda,
B.M.Dunn,
A.Wlodawer,
and
T.Nakayama
(2006).
Processing, catalytic activity and crystal structures of kumamolisin-As with an engineered active site.
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FEBS J,
273,
2563-2576.
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PDB codes:
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Q.Xu,
H.Guo,
A.Wlodawer,
and
H.Guo
(2006).
The importance of dynamics in substrate-assisted catalysis and specificity.
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J Am Chem Soc,
128,
5994-5995.
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Y.Tian,
I.Sohar,
J.W.Taylor,
and
P.Lobel
(2006).
Determination of the substrate specificity of tripeptidyl-peptidase I using combinatorial peptide libraries and development of improved fluorogenic substrates.
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J Biol Chem,
281,
6559-6572.
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S.E.Mole,
R.E.Williams,
and
H.H.Goebel
(2005).
Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses.
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Neurogenetics,
6,
107-126.
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A.A.Golabek,
P.Wujek,
M.Walus,
S.Bieler,
C.Soto,
K.E.Wisniewski,
and
E.Kida
(2004).
Maturation of human tripeptidyl-peptidase I in vitro.
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J Biol Chem,
279,
31058-31067.
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A.Wlodawer,
M.Li,
A.Gustchina,
N.Tsuruoka,
M.Ashida,
H.Minakata,
H.Oyama,
K.Oda,
T.Nishino,
and
T.Nakayama
(2004).
Crystallographic and biochemical investigations of kumamolisin-As, a serine-carboxyl peptidase with collagenase activity.
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J Biol Chem,
279,
21500-21510.
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PDB codes:
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A.Wlodawer
(2004).
How to kill an enzyme (in more ways than one).
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Structure,
12,
1117-1119.
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C.DeWeese-Scott,
and
J.Moult
(2004).
Molecular modeling of protein function regions.
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Proteins,
55,
942-961.
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I.Botos,
E.E.Melnikov,
S.Cherry,
J.E.Tropea,
A.G.Khalatova,
F.Rasulova,
Z.Dauter,
M.R.Maurizi,
T.V.Rotanova,
A.Wlodawer,
and
A.Gustchina
(2004).
The catalytic domain of Escherichia coli Lon protease has a unique fold and a Ser-Lys dyad in the active site.
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J Biol Chem,
279,
8140-8148.
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PDB codes:
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M.Fujinaga,
M.M.Cherney,
H.Oyama,
K.Oda,
and
M.N.James
(2004).
The molecular structure and catalytic mechanism of a novel carboxyl peptidase from Scytalidium lignicolum.
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Proc Natl Acad Sci U S A,
101,
3364-3369.
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PDB codes:
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N.Andreeva,
P.Bogdanovich,
I.Kashparov,
M.Popov,
and
M.Stengach
(2004).
Is histoaspartic protease a serine protease with a pepsin-like fold?
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Proteins,
55,
705-710.
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PDB code:
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P.Wujek,
E.Kida,
M.Walus,
K.E.Wisniewski,
and
A.A.Golabek
(2004).
N-glycosylation is crucial for folding, trafficking, and stability of human tripeptidyl-peptidase I.
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J Biol Chem,
279,
12827-12839.
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A.Wlodawer,
S.R.Durell,
M.Li,
H.Oyama,
K.Oda,
and
B.M.Dunn
(2003).
A model of tripeptidyl-peptidase I (CLN2), a ubiquitous and highly conserved member of the sedolisin family of serine-carboxyl peptidases.
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BMC Struct Biol,
3,
8.
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PDB code:
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N.Tsuruoka,
T.Nakayama,
M.Ashida,
H.Hemmi,
M.Nakao,
H.Minakata,
H.Oyama,
K.Oda,
and
T.Nishino
(2003).
Collagenolytic serine-carboxyl proteinase from Alicyclobacillus sendaiensis strain NTAP-1: purification, characterization, gene cloning, and heterologous expression.
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Appl Environ Microbiol,
69,
162-169.
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M.Comellas-Bigler,
P.Fuentes-Prior,
K.Maskos,
R.Huber,
H.Oyama,
K.Uchida,
B.M.Dunn,
K.Oda,
and
W.Bode
(2002).
The 1.4 a crystal structure of kumamolysin: a thermostable serine-carboxyl-type proteinase.
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Structure,
10,
865-876.
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PDB codes:
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N.T.Hoa,
J.A.Brannigan,
and
S.M.Cutting
(2002).
The Bacillus subtilis signaling protein SpoIVB defines a new family of serine peptidases.
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J Bacteriol,
184,
191-199.
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C.Venclovas
(2001).
Comparative modeling of CASP4 target proteins: combining results of sequence search with three-dimensional structure assessment.
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Proteins,
(),
47-54.
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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
