PDBsum entry 2z4e

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protein ligands metals Protein-protein interface(s) links
Blood clotting PDB id
Jmol PyMol
Protein chains
67 a.a. *
303 a.a. *
292 a.a. *
54 a.a. *
NAG ×2
_CA ×8
* Residue conservation analysis
PDB id:
Name: Blood clotting
Title: Crystal structure of d-dimer from human fibrin complexed wit arg-pro-tyr-amide
Structure: Fibrinogen alpha chain. Chain: a, d. Fragment: residues in database 130-218. Fibrinogen beta chain. Chain: b, e. Fragment: residues in database 164-491. Fibrinogen, gamma polypeptide. Chain: c, f. Fragment: residues in database 114-437.
Source: Homo sapiens. Human. Organism_taxid: 9606. Synthetic: yes. Other_details: the sequence occurs naturally in humans.. Other_details: the sequence occurs naturally in bovines (e. Taurus).
2.70Å     R-factor:   0.216     R-free:   0.275
Authors: R.F.Doolittle,L.Pandi
Key ref: R.F.Doolittle and L.Pandi (2007). Probing the beta-chain hole of fibrinogen with synthetic peptides that differ at their amino termini. Biochemistry, 46, 10033-10038. PubMed id: 17688324
16-Jun-07     Release date:   23-Oct-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P02671  (FIBA_HUMAN) -  Fibrinogen alpha chain
866 a.a.
67 a.a.
Protein chains
Pfam   ArchSchema ?
P02675  (FIBB_HUMAN) -  Fibrinogen beta chain
491 a.a.
303 a.a.
Protein chains
Pfam   ArchSchema ?
P02679  (FIBG_HUMAN) -  Fibrinogen gamma chain
453 a.a.
292 a.a.
Protein chain
Pfam   ArchSchema ?
P02671  (FIBA_HUMAN) -  Fibrinogen alpha chain
866 a.a.
54 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     fibrinogen complex   1 term 
  Biological process     signal transduction   3 terms 
  Biochemical function     receptor binding     2 terms  


Biochemistry 46:10033-10038 (2007)
PubMed id: 17688324  
Probing the beta-chain hole of fibrinogen with synthetic peptides that differ at their amino termini.
R.F.Doolittle, L.Pandi.
In a recent report, we showed that alanine can replace glycine at the amino terminus of synthetic B-knobs that bind to human fibrin(ogen). We now report a survey of 13 synthetic peptides with the general sequence XHRPYam, all tested with regard to their ability to delay fibrinolysis in an in vitro system activated by t-PA, the results being used as measures of binding affinity to the betaC hole. Unexpectedly, some large and bulky amino acids, including methionine and arginine, are effective binders. Amino acids that branch at the beta carbon (valine, isoleucine, and threonine) do not bind effectively. Crystal structures were determined for two of the peptides (GHRPYam and MHRPYam) complexed with fibrin fragment D-dimer; the modeling of various other side chains showed clashing in the cases of beta-carbon substituents. The two crystal structures also showed that the enhanced binding observed with pentapeptides with carboxyl-terminal tyrosine, compared with that of their tetrapeptide equivalents, is attributable to an interaction between the tyrosine side chain and a guanidino group of a nearby arginine (beta406). The equivalent position in gamma-chains of human fibrin(ogen) is occupied by a lysine (gamma338), but in chicken and lamprey fibrin(ogen), it is an arginine, just as occurs in beta chains. Accordingly, the peptides GPRPam and GPRPYam, which are surrogate A-knobs, were tested for their influence on fibrin polymerization with fibrinogen from lamprey and humans. In lampreys, GPRPYam is a significantly better inhibitor, but in humans, it is less effective than GPRPam, indicating that in the lamprey system the same tyrosine-arginine interaction can also occur in the gamma-chain setting.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20484082 S.E.Stabenfeldt, J.J.Gossett, and T.H.Barker (2010).
Building better fibrin knob mimics: an investigation of synthetic fibrin knob peptide structures in solution and their dynamic binding with fibrinogen/fibrin holes.
  Blood, 116, 1352-1359.  
19797520 R.A.Campbell, K.A.Overmyer, C.H.Selzman, B.C.Sheridan, and A.S.Wolberg (2009).
Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability.
  Blood, 114, 4886-4896.  
19075185 S.R.Bowley, and S.T.Lord (2009).
Fibrinogen variant BbetaD432A has normal polymerization but does not bind knob "B".
  Blood, 113, 4425-4430.
PDB code: 3e1i
19008457 S.S.Adam, N.S.Key, and C.S.Greenberg (2009).
D-dimer antigen: current concepts and future prospects.
  Blood, 113, 2878-2887.  
18987303 W.G.Kerrick, K.Kazmierczak, Y.Xu, Y.Wang, and D.Szczesna-Cordary (2009).
Malignant familial hypertrophic cardiomyopathy D166V mutation in the ventricular myosin regulatory light chain causes profound effects in skinned and intact papillary muscle fibers from transgenic mice.
  FASEB J, 23, 855-865.  
17922803 J.W.Weisel (2007).
Which knobs fit into which holes in fibrin polymerization?
  J Thromb Haemost, 5, 2340-2343.  
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 code is shown on the right.