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PDBsum entry 1eai
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Serine proteinase
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PDB id
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1eai
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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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The molecular structure of the complex of ascaris chymotrypsin/elastase inhibitor with porcine elastase.
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Authors
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K.Huang,
N.C.Strynadka,
V.D.Bernard,
R.J.Peanasky,
M.N.James.
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Ref.
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Structure, 1994,
2,
679-689.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: The intestinal parasitic worm, Ascaris suum, produces a variety of
protein inhibitors that defend the organism against the host's proteinases.
Eight different proteins from Ascaris suum have been identified as inhibitors of
serine proteinases, targeting chymotrypsin, elastase and trypsin. These
inhibitors share 30-40% sequence identity with one another, but have virtually
no sequence identity with members of any of the other families of serine
proteinase inhibitors. RESULTS: The crystal structure of the complex of porcine
pancreatic elastase with a chymotrypsin/elastase inhibitor from Ascaris suum
(the C/E-1 inhibitor) has been solved to 2.4 A resolution by the molecular
replacement method. The C/E-1 inhibitor exhibits a novel folding motif. There
are only two small beta-sheets and two single-turn 3(10)-helices in this
inhibitor. Unlike the majority of proteins, the C/E-1 inhibitor does not have a
hydrophobic core. The presence and unique topography of the five disulfide
bridges suggests that they play important roles in maintaining the tertiary
structure of the inhibitor. In addition, the side chains of several charged
residues from electrostatic and hydrogen-bonding cascades, which also probably
compensate for the lack of extensive secondary structures and a hydrophobic
core. The reactive-site loop of this inhibitor displays a conformation that is
characteristic of most serine proteinase inhibitors. CONCLUSIONS: The structure
of the C/E-1 inhibitor confirms that inhibitors from Ascaris suum belong to a
novel family of proteinase inhibitors. It also provides conclusive evidence for
the correct disulfide bridge connections. The C/E-1 inhibitor probably acts by a
common inhibitory mechanism proposed for other substrate-like protein inhibitors
of serine proteinases. The unusual molecular scaffolding presents a challenge to
current folding algorithms. Proteins like the C/E-1 inhibitor may provide a
valuable model system to study how the primary sequence of a protein dictates
its three-dimensional structure.
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Figure 4.
Figure 4. The salt bridge/hydrogen-bond network centered on
Arg48 I. The side chain of Arg48 I, and the peptide nitrogen
atoms of Gly6 I and Cys40 I are shown in blue. The side chain of
Glu9 I, the side chain of Glu18 I and the peptide oxygen of
Gly52 I are shown in red. Dashed lines represent hydrogen bonds
or salt bridges within 3.2 å. Figure 4. The salt
bridge/hydrogen-bond network centered on Arg48 I. The side chain
of Arg48 I, and the peptide nitrogen atoms of Gly6 I and Cys40 I
are shown in blue. The side chain of Glu9 I, the side chain of
Glu18 I and the peptide oxygen of Gly52 I are shown in red.
Dashed lines represent hydrogen bonds or salt bridges within 3.2
å.
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Figure 7.
Figure 7. Superposition of residues P [3]to P [2]′ of the
reactive-site loops from a selection of protein inhibitors of
serine proteinases. The C/E-1 inhibitor is shown in green,
bovine pancreatic trypsin inhibitor (BPTI) in yellow, ovomucoid
inhibitor third domain from turkey (OMTKY3) in red, chymotrypsin
inhibitor-1 from potato (PCI-1) in cyan, leech inhibitor
eglin-c in purple and Bowman–Birk inhibitor from beans in
pink. Figure 7. Superposition of residues P [3]to P [2]′ of
the reactive-site loops from a selection of protein inhibitors
of serine proteinases. The C/E-1 inhibitor is shown in green,
bovine pancreatic trypsin inhibitor (BPTI) in yellow, ovomucoid
inhibitor third domain from turkey (OMTKY3) in red, chymotrypsin
inhibitor-1 from potato (PCI-1) in cyan, leech inhibitor eglin-c
in purple and Bowman–Birk inhibitor from beans in pink.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(1994,
2,
679-689)
copyright 1994.
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Secondary reference #1
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Title
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Structure of native porcine pancreatic elastase at 1.65 resolution
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Authors
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E.Meyer,
G.Cole,
R.Radharkrishnan.
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Ref.
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acta crystallogr ,sect b, 1988,
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22.
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