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PDBsum entry 1pfg
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Hydrolase/hydrolase inhibitor
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PDB id
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1pfg
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.21.64
- peptidase K.
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Reaction:
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Hydrolysis of keratin and of other proteins, with subtilisin-like specificity. Hydrolyzes peptides amides.
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DOI no:
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Protein Sci
5:2453-2458
(1996)
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PubMed id:
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Strategy to design peptide inhibitors: structure of a complex of proteinase K with a designed octapeptide inhibitor N-Ac-Pro-Ala-Pro-Phe-DAla-Ala-Ala-Ala-NH2 at 2.5 A resolution.
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A.K.Saxena,
T.P.Singh,
K.Peters,
S.Fittkau,
C.Betzel.
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ABSTRACT
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The crystal structure of a complex formed by the interaction between proteinase
K and a designed octapeptide amide, N-Ac-Pro-Ala-Pro-Phe-DAla-Ala-Ala-Ala-NH2,
has been determined at 2.5 A resolution and refined to an R-factor of 16.7% for
7,430 reflections in the resolution range of 8.0-2.50 A. The inhibitor forms a
stable complex through a series of hydrogen bonds and hydrophobic interactions
with the protein atoms and water molecules. The inhibitor is hydrolyzed between
Phe4I and DAla5I (I indicates the inhibitor). The two fragments are separated by
a distance of 3.2 A between the carbonyl carbon of Phe4I and the main-chain
nitrogen of DAla5I. The N-terminal tetrapeptide occupies subsites S1-S5 (S5 for
acetyl group), whereas the C-terminal part fits into S1'-S5' region (S5' for
amide group). It is the first time that such an extended electron density for a
designed synthetic peptide inhibitor has been observed in the prime region of an
enzyme of the subtilisin family. In fact, the inhibitor fills the recognition
site completely. There is only a slight rearrangement of the protein residues to
accommodate the inhibitor. Superposition of the present octapeptide inhibitor on
the hexapeptide inhibitor studied previously shows an overall homology of the
two inhibitors, although the individual atoms are displaced significantly. It
suggests the existence of a recognition site with flexible dimensions. Kinetic
studies indicate an inhibition rate of 100% by this specifically designed
peptide inhibitor.
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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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S.B.Larson,
J.S.Day,
C.Nguyen,
R.Cudney,
and
A.McPherson
(2009).
High-resolution structure of proteinase K cocrystallized with digalacturonic acid.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
65,
192-198.
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PDB code:
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P.Ingallinella,
D.Fattori,
S.Altamura,
C.Steinkühler,
U.Koch,
D.Cicero,
R.Bazzo,
R.Cortese,
E.Bianchi,
and
A.Pessi
(2002).
Prime site binding inhibitors of a serine protease: NS3/4A of hepatitis C virus.
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Biochemistry,
41,
5483-5492.
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C.Betzel,
S.Gourinath,
P.Kumar,
P.Kaur,
M.Perbandt,
S.Eschenburg,
and
T.P.Singh
(2001).
Structure of a serine protease proteinase K from Tritirachium album limber at 0.98 A resolution.
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Biochemistry,
40,
3080-3088.
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PDB code:
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P.Ingallinella,
E.Bianchi,
R.Ingenito,
U.Koch,
C.Steinkühler,
S.Altamura,
and
A.Pessi
(2000).
Optimization of the P'-region of peptide inhibitors of hepatitis C virus NS3/4A protease.
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Biochemistry,
39,
12898-12906.
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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
