 |
PDBsum entry 4zhm
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase inhibitor/hydrolase
|
PDB id
|
|
|
|
4zhm
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Selection of high-Affinity peptidic serine protease inhibitors with increased binding entropy from a back-Flip library of peptide-Protease fusions.
|
|
|
Authors
|
|
H.P.Sørensen,
P.Xu,
L.Jiang,
T.Kromann-Hansen,
K.J.Jensen,
M.Huang,
P.A.Andreasen.
|
|
|
Ref.
|
|
J Mol Biol, 2015,
427,
3110-3122.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
We have developed a new concept for designing peptidic protein modulators, by
recombinantly fusing the peptidic modulator, with randomized residues, directly
to the target protein via a linker and screening for internal modulation of the
activity of the protein. We tested the feasibility of the concept by fusing a
10-residue-long, disulfide-bond-constrained inhibitory peptide, randomized in
selected positions, to the catalytic domain of the serine protease murine
urokinase-type plasminogen activator. High-affinity inhibitory peptide variants
were identified as those that conferred to the fusion protease the lowest
activity for substrate hydrolysis. The usefulness of the strategy was
demonstrated by the selection of peptidic inhibitors of murine urokinase-type
plasminogen activator with a low nanomolar affinity. The high affinity could not
have been predicted by rational considerations, as the high affinity was
associated with a loss of polar interactions and an increased binding entropy.
|
|
|
|
|
|
|
