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PDBsum entry 4dw2
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Hydrolase/immune system
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PDB id
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4dw2
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Contents |
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221 a.a.
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210 a.a.
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214 a.a.
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References listed in PDB file
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Key reference
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Title
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Rezymogenation of active urokinase induced by an inhibitory antibody.
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Authors
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L.Jiang,
K.A.Botkjaer,
L.M.Andersen,
C.Yuan,
P.A.Andreasen,
M.Huang.
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Ref.
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Biochem J, 2013,
449,
161-166.
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PubMed id
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Abstract
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An important regulatory mechanism of serine proteases is the proteolytic
conversion of the inactive pro-enzyme, or zymogen, into the active enzyme. This
activation process is generally considered an irreversible process. In the
present study, we demonstrate that an active enzyme can be converted back into
its zymogen form. We determined the crystal structure of uPA (urokinase-type
plasminogen activator) in complex with an inhibitory antibody, revealing that
the antibody 'rezymogenizes' already activated uPA. The present study
demonstrates a new regulatory mechanism of protease activity, which is also an
extreme case of protein allostery. Mechanistically, the antibody binds a single
surface-exposed loop, named the autolysis loop, thereby preventing the
stabilization of uPA in its active conformation. We argue that this autolysis
loop is a key structural element for rezymogenation of other proteases, and will
be a new target site for pharmacological intervention with serine protease
activity.
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