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Blood clotting PDB id
2h43
Jmol
Contents
Protein chains
70 a.a. *
302 a.a. *
290 a.a. *
Ligands
ALA-HIS-ARG-PRO-
NH2
×2
NAG-NAG
NAG-NDG
Metals
_CA ×6
* Residue conservation analysis
PDB id:
2h43
Name: Blood clotting
Title: Crystal structure of human fragment d complexed with ala-his amide
Structure: Fibrinogen alpha chain. Chain: a, d. Fibrinogen beta chain. Chain: b, e. Fibrinogen gamma chain. Chain: c, f. Gly-his-arg-pro-amide peptide ligand. Chain: i, j. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Synthetic: yes. Other_details: the peptide was chemically synthesized.
Biol. unit: Tetramer (from PQS)
Resolution:
2.70Å     R-factor:   0.251     R-free:   0.307
Authors: R.F.Doolittle,L.Pandi
Key ref:
R.F.Doolittle et al. (2006). Differences in binding specificity for the homologous gamma- and beta-chain "holes" on fibrinogen: exclusive binding of Ala-His-Arg-Pro-amide by the beta-chain hole. Biochemistry, 45, 13962-13969. PubMed id: 17115691 DOI: 10.1021/bi061219e
Date:
23-May-06     Release date:   05-Dec-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P02671  (FIBA_HUMAN) -  Fibrinogen alpha chain
Seq:
Struc:
 
Seq:
Struc:
866 a.a.
70 a.a.
Protein chains
Pfam   ArchSchema ?
P02675  (FIBB_HUMAN) -  Fibrinogen beta chain
Seq:
Struc:
491 a.a.
302 a.a.
Protein chains
Pfam   ArchSchema ?
P02679  (FIBG_HUMAN) -  Fibrinogen gamma chain
Seq:
Struc:
453 a.a.
290 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   2 terms 
  Biological process     signal transduction   3 terms 
  Biochemical function     receptor binding     2 terms  

 

 
DOI no: 10.1021/bi061219e Biochemistry 45:13962-13969 (2006)
PubMed id: 17115691  
 
 
Differences in binding specificity for the homologous gamma- and beta-chain "holes" on fibrinogen: exclusive binding of Ala-His-Arg-Pro-amide by the beta-chain hole.
R.F.Doolittle, A.Chen, L.Pandi.
 
  ABSTRACT  
 
The beta-chain amino-terminal sequences of all known mammalian fibrins begin with the sequence Gly-His-Arg-Pro- (GHRP-), but the homologous sequence in chicken fibrin begins with the sequence Ala-His-Arg-Pro- (AHRP-). Nonetheless, chicken fibrinogen binds the synthetic peptide GHRPam, and a previously reported crystal structure has revealed that the binding is in exact conformance with that observed for the human GHRPam-fragment D complex. We now report that human fibrinogen, which is known not to bind APRP, binds the synthetic peptide AHRPam. Moreover, a crystal structure of AHRPam complexed with fragment D from human fibrinogen shows that AHRPam binds exclusively to the beta-chain hole and, unlike GHRPam, not at all to the homologous gamma-chain hole. The difference can be attributed to the methyl group of the alanine residue clashing with a critical carboxyl group in the gammaC hole but being accommodated in the roomier betaC hole where the equivalent carboxyl is situated more flexibly.
 

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.  
18818200 I.Parastatidis, L.Thomson, A.Burke, I.Chernysh, C.Nagaswami, J.Visser, S.Stamer, D.C.Liebler, G.Koliakos, H.F.Heijnen, G.A.Fitzgerald, J.W.Weisel, and H.Ischiropoulos (2008).
Fibrinogen beta-chain tyrosine nitration is a prothrombotic risk factor.
  J Biol Chem, 283, 33846-33853.  
17892530 C.B.Geer, A.Tripathy, M.H.Schoenfisch, S.T.Lord, and O.V.Gorkun (2007).
Role of 'B-b' knob-hole interactions in fibrin binding to adsorbed fibrinogen.
  J Thromb Haemost, 5, 2344-2351.  
17952642 M.Guthold, W.Liu, E.A.Sparks, L.M.Jawerth, L.Peng, M.Falvo, R.Superfine, R.R.Hantgan, and S.T.Lord (2007).
A comparison of the mechanical and structural properties of fibrin fibers with other protein fibers.
  Cell Biochem Biophys, 49, 165-181.  
17414213 S.T.Lord (2007).
Fibrinogen and fibrin: scaffold proteins in hemostasis.
  Curr Opin Hematol, 14, 236-241.  
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.