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PDBsum entry 1k9o
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Hydrolase/hydrolase inhibitor
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PDB id
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1k9o
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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 structure of a michaelis serpin-Protease complex.
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Authors
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S.Ye,
A.L.Cech,
R.Belmares,
R.C.Bergstrom,
Y.Tong,
D.R.Corey,
M.R.Kanost,
E.J.Goldsmith.
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Ref.
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Nat Struct Biol, 2001,
8,
979-983.
[DOI no: ]
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PubMed id
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Abstract
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Serine protease inhibitors (serpins) regulate the activities of circulating
proteases. Serpins inhibit proteases by acylating the serine hydroxyl at their
active sites. Before deacylation and complete proteolysis of the serpin can
occur, massive conformational changes are triggered in the serpin while
maintaining the covalent linkage between the protease and serpin. Here we report
the structure of a serpin-trypsin Michaelis complex, which we visualized by
using the S195A trypsin mutant to prevent covalent complex formation. This
encounter complex reveals a more extensive interaction surface than that present
in small inhibitor-protease complexes and is a template for modeling other
serpin-protease pairs. Mutations of several serpin residues at the interface
reduced the inhibitory activity of the serpin. The serine residue C-terminal to
the scissile peptide bond is found in a closer than usual interaction with His
57 at the active site of trypsin.
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Figure 1.
Figure 1. Overall structure of serpin-protease complex and
comparison with other serpins. a, Ribbon diagram of serpin 1B
A353K -trypsin S195A complex. RCL is gold; helices of both
serpin and trypsin are blue;  -sheets
A, B and C of the serpin are light, medium and dark magenta,
respectively; and -sheets
of trypsin S195A are red. b, Superposition of active serpin 1K
(PDB code 1SEK) (cyan throughout; red reactive center) with
serpin 1B A353K (magenta throughout; gold reactive center). c,
Cleaved form of the serpin  -1
antitrypsin (PDB code 9API) drawn by BOBSCRIPT31 and rendered by
POV-RAY32. The topological switch point at P16 for insertion of
the RCL as strand 4A is marked in (b,c).
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Figure 3.
Figure 3. Stereo diagram showing interactions between P16 and P8
in RCL (see text).
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2001,
8,
979-983)
copyright 2001.
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