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PDBsum entry 1sfi
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Hydrolase/hydrolase inhibitor
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PDB id
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1sfi
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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High-Resolution structure of a potent, Cyclic proteinase inhibitor from sunflower seeds.
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Authors
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S.Luckett,
R.S.Garcia,
J.J.Barker,
A.V.Konarev,
P.R.Shewry,
A.R.Clarke,
R.L.Brady.
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Ref.
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J Mol Biol, 1999,
290,
525-533.
[DOI no: ]
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PubMed id
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Abstract
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Proteinaceous serine proteinase inhibitors are widespread throughout the plant
kingdom where they play an important role in protection against pests and
pathogens. Here, we describe the isolation and characterisation of a novel 14
amino acid residue cyclic peptide from sunflower seeds, which is a potent
inhibitor of trypsin (Ki=100 pM). The crystal structure of this peptide in
complex with bovine beta-trypsin shows both sequence and conformational
similarity with the trypsin-reactive loop of the Bowman-Birk family of serine
proteinase inhibitors. This inhibitor, however, is unique in being
monofunctional, cyclic and far shorter (14 amino acid residues) than inhibitors
belonging to this family (typically 60-70 amino acid residues). The high potency
of this peptide is likely to arise from the considerable structural rigidity
achieved through its cyclic nature which is further stabilised by a single
internal disulphide bond. This study helps delineate the minimal unit required
for effective peptide inhibitors of serine proteinases, and will assist in the
further design of inhibitors to this widespread class of enzymes.
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Figure 4.
Figure 4. C
a
traces showing
superimpositions of SFTI-1 (red)
with the Mung bean inhibitor (Li
et al., 1994) shown in blue, Adzuki
bean inhibitor (Tsunogae et al.,
1986) shown in yellow, and soy-
bean inhibitor (Werner & Wemmer,
1992) shown in green. The P1
lysine residue is indicated.
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Figure 5.
Figure 5. Stereoview showing the
interactions of the active site loop
of the inhibitor with bovine trypsin.
Lys5-I projects into the S1 pocket
of the enzyme, delineating speci-
ficity for trypsin-like serine protein-
ases. SFTI-1 residues are shown in
yellow and ordered water mol-
ecules in red.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1999,
290,
525-533)
copyright 1999.
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