1fge
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EPIDERMAL GROWTH FACTOR (EGF) SUBDOMAIN OF HUMAN THROMBOMODULIN (NMR, 14 STRUCTURES)
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Myocardial infarction, susceptibility to OMIM:[188040], Thrombophilia due to thrombomodulin defect OMIM:[188040]
About this StructureAbout this Structure
1FGE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural resiliency of an EGF-like subdomain bound to its target protein, thrombin., Hrabal R, Komives EA, Ni F, Protein Sci. 1996 Feb;5(2):195-203. PMID:8745396
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