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PDBsum entry 1fgd

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protein links
Blood coagulation inhibitor PDB id
1fgd
Jmol
Contents
Protein chain
18 a.a.
PDB id:
1fgd
Name: Blood coagulation inhibitor
Title: Epidermal growth factor (egf) subdomain of human thrombomodulin (nmr, 11 structures)
Structure: Thrombomodulin. Chain: a. Fragment: c-terminal subdomain, residues 409 - 426, of 5th epidermal growth factor (egf). Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
NMR struc: 11 models
Authors: R.Hrabal,E.A.Komives,F.Ni
Key ref: R.Hrabal et al. (1996). Structural resiliency of an EGF-like subdomain bound to its target protein, thrombin. Protein Sci, 5, 195-203. PubMed id: 8745396 DOI: 10.1002/pro.5560050202
Date:
28-Nov-95     Release date:   20-Jun-96    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P07204  (TRBM_HUMAN) -  Thrombomodulin
Seq:
Struc:
 
Seq:
Struc:
575 a.a.
18 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to membrane   1 term 
  Biochemical function     transmembrane signaling receptor activity     1 term  

 

 
DOI no: 10.1002/pro.5560050202 Protein Sci 5:195-203 (1996)
PubMed id: 8745396  
 
 
Structural resiliency of an EGF-like subdomain bound to its target protein, thrombin.
R.Hrabal, E.A.Komives, F.Ni.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
15049836 G.Isetti, and M.C.Maurer (2004).
Probing thrombin's ability to accommodate a V34F substitution within the factor XIII activation peptide segment (28-41).
  J Pept Res, 63, 241-252.  
12434426 J.Song, P.Xu, A.Koutychenko, and F.Ni (2002).
Stability of protein-bound conformations of bioactive peptides: the folded conformation of an epidermal growth factor-like thrombomodulin fragment is similar to that recognized by thrombin.
  Biopolymers, 65, 373-386.  
11381118 T.Scherf, R.Kasher, M.Balass, M.Fridkin, S.Fuchs, and E.Katchalski-Katzir (2001).
A beta -hairpin structure in a 13-mer peptide that binds alpha -bungarotoxin with high affinity and neutralizes its toxicity.
  Proc Natl Acad Sci U S A, 98, 6629-6634.
PDB codes: 1haa 1haj
10956026 D.Tolkatchev, A.Ng, B.Zhu, and F.Ni (2000).
Identification of a thrombin-binding region in the sixth epidermal growth factor-like repeat of human thrombomodulin.
  Biochemistry, 39, 10365-10372.  
10336381 M.C.Maurer, J.Y.Trosset, C.C.Lester, E.E.DiBella, and H.A.Scheraga (1999).
New general approach for determining the solution structure of a ligand bound weakly to a receptor: structure of a fibrinogen Aalpha-like peptide bound to thrombin (S195A) obtained using NOE distance constraints and an ECEPP/3 flexible docking program.
  Proteins, 34, 29-48.  
9636055 D.Tolkatchev, and F.Ni (1998).
Calcium binding properties of an epidermal growth factor-like domain from human thrombomodulin.
  Biochemistry, 37, 9091-9100.  
9843953 J.G.Mandell, A.M.Falick, and E.A.Komives (1998).
Identification of protein-protein interfaces by decreased amide proton solvent accessibility.
  Proc Natl Acad Sci U S A, 95, 14705-14710.  
8816772 C.E.White, M.J.Hunter, D.P.Meininger, S.Garrod, and E.A.Komives (1996).
The fifth epidermal growth factor-like domain of thrombomodulin does not have an epidermal growth factor-like disulfide bonding pattern.
  Proc Natl Acad Sci U S A, 93, 10177-10182.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.