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PDBsum entry 1dpj
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Hydrolase/hydrolase inhibitor
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PDB id
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1dpj
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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 aspartic proteinase from saccharomyces cerevisiae folds its own inhibitor into a helix.
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Authors
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M.Li,
L.H.Phylip,
W.E.Lees,
J.R.Winther,
B.M.Dunn,
A.Wlodawer,
J.Kay,
A.Gustchina.
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Ref.
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Nat Struct Biol, 2000,
7,
113-117.
[DOI no: ]
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PubMed id
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Abstract
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Aspartic proteinase A from yeast is specifically and potently inhibited by a
small protein called IA3 from Saccharomyces cerevisiae. Although this inhibitor
consists of 68 residues, we show that the inhibitory activity resides within the
N-terminal half of the molecule. Structures solved at 2.2 and 1.8 A,
respectively, for complexes of proteinase A with full-length IA3 and with a
truncated form consisting only of residues 2-34, reveal an unprecedented mode of
inhibitor-enzyme interactions. Neither form of the free inhibitor has detectable
intrinsic secondary structure in solution. However, upon contact with the
enzyme, residues 2-32 become ordered and adopt a near-perfect alpha-helical
conformation. Thus, the proteinase acts as a folding template, stabilizing the
helical conformation in the inhibitor, which results in the potent and specific
blockage of the proteolytic activity.
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Figure 1.
Figure 1. Schematic diagram of the structure of proteinase A.
Ribbon representation showing the tracing of the main chain of
proteinase A (green) with the oligosaccharide attached to Asn 67
shown in mauve, together with the visible fragment of the
inhibitor IA[3] (gold). Side chains of the active site residues
Asp 32 and Asp 215 are shown in red.
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Figure 3.
Figure 3. Interactions in the vicinity of the active site of
proteinase A. Proteinase A (green, with the active site
aspartates red) complexed to IA[3] (yellow with orange side
chains) is superimposed on progastricsin (purple). Water
molecules in the proteinase A complex are blue, and hydrogen
bonds are marked as thin lines.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2000,
7,
113-117)
copyright 2000.
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Secondary reference #1
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Title
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The three-Dimensional structure at 2.4 a resolution of glycosylated proteinase a from the lysosome-Like vacuole of saccharomyces cerevisiae.
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Authors
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C.F.Aguilar,
N.B.Cronin,
M.Badasso,
T.Dreyer,
M.P.Newman,
J.B.Cooper,
D.J.Hoover,
S.P.Wood,
M.S.Johnson,
T.L.Blundell.
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Ref.
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J Mol Biol, 1997,
267,
899-915.
[DOI no: ]
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PubMed id
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Figure 5.
Figure 5. Electrostatic potential of proteinase A sampled at the molecular surface of the enzyme with a probe sphere
of radius 1.4 Å (blue, basic; red, acidic) generated using DELPHI (Sharp & Nicholls, 1990).
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Figure 7.
Figure 7. Interactions between enzyme and inhibitor; least squares superposition of the complex of yeast proteinase
A-CP-81,282 and the complex of endothiapepsin CP-81,282 (Veerapandian et al., 1992).
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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