 |
PDBsum entry 1fgd
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Blood coagulation inhibitor
|
PDB id
|
|
|
|
1fgd
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural resiliency of an egf-Like subdomain bound to its target protein, Thrombin.
|
|
|
Authors
|
|
R.Hrabal,
E.A.Komives,
F.Ni.
|
|
|
Ref.
|
|
Protein Sci, 1996,
5,
195-203.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The thrombin-bound structures of native peptide fragments from the fifth
EGF-like domain of thrombomodulin were determined by use of NMR and transferred
NOE spectroscopy. The bound peptides assume an EGF-like structure of an
antiparallel beta-sheet, a novel structural motif observed for a bound peptide
in protein-peptide complexes. There is a remarkable structural resiliency of
this structure motif manifested in its ability to accommodate a different number
of residues within the disulfide loop. Docking experiments revealed that the key
contacts with thrombin are hydrophobic interactions between the side chains of
residues Ile 414 and Ile 424 of thrombomodulin and a hydrophobic pocket on the
thrombin surface. Residues Leu 415, Phe 419, and Ile 420, which would have been
buried in intact EGF-like domains, are unfavorably exposed in the complex of
thrombin with the EGF-like thrombomodulin fragment, thus providing a rationale
for the enhancement of binding affinity upon the deletion of Ile 420. The unique
beta-sheet structures of the bound peptides are specified by the presence of
disulfide bridges in the peptides because a corresponding linear thrombomodulin
fragment folds into a sheet structure with a different backbone topology. The
different bound conformations for the linear and the cyclized peptides indicate
that side-chain interactions within a specific environment may dictate the
folding of bound peptides in protein-peptide complexes.
|
|
|
|
|
|
|
