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PDBsum entry 1sek
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Serine protease inhibitor
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PDB id
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1sek
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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 active serpin 1k from manduca sexta.
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Authors
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J.Li,
Z.Wang,
B.Canagarajah,
H.Jiang,
M.Kanost,
E.J.Goldsmith.
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Ref.
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Structure, 1999,
7,
103-109.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: The reactive center loops (RCL) of serpins undergo large
conformational changes triggered by the interaction with their target protease.
Available crystallographic data suggest that the serpin RCL is polymorphic, but
the relevance of the observed conformations to the competent active structure
and the conformational changes that occur on binding target protease has
remained obscure. New high-resolution data on an active serpin, serpin 1K from
the moth hornworm Manduca sexta, provide insights into how active serpins are
stabilized and how conformational changes are induced by protease binding.
RESULTS: The 2.1 A structure shows that the RCL of serpin 1K, like that of
active alpha1-antitrypsin, is canonical, complimentary and ready to bind to the
target protease between P3 and P3 (where P refers to standard protease
nomenclature),. In the hinge region (P17-P13), however, the RCL of serpin 1K,
like ovalbumin and alpha1-antichymotrypsin, forms tight interactions that
stabilize the five-stranded closed form of betasheet A. These interactions are
not present in, and are not compatible with, the observed structure of active
alpha1-antitrypsin. CONCLUSIONS: Serpin 1K may represent the best resting
conformation for serpins - canonical near P1, but stabilized in the closed
conformation of betasheet A. By comparison with other active serpins, especially
alpha1-antitrypsin, a model is proposed in which interaction with the target
protease near P1 leads to conformational changes in betasheet A of the serpin.
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Figure 5.
Figure 5. The RCL of serpin 1K. (a) Stereo diagram showing
interactions of the hinge (P[17]–P[13]) in the RCL with
ts3AhF1, thDs2A, and ts2Bs3B. Water molecules are shown as cyan
spheres. (b) Ribbon diagram corresponding to (a).
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1999,
7,
103-109)
copyright 1999.
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