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PDBsum entry 1ltj
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protein ligands metals Protein-protein interface(s) links
Blood clotting PDB id
1ltj

 

 

 

 

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Contents
Protein chains
65 a.a. *
298 a.a. *
299 a.a. *
58 a.a. *
Ligands
GLY-PRO-ARG-PRO ×2
GLY-HIS-ARG-PRO ×2
NAG-NAG-FUC ×2
Metals
_CA ×4
Waters ×250
* Residue conservation analysis
PDB id:
1ltj
Name: Blood clotting
Title: Crystal structure of recombinant human fibrinogen fragment d with the peptide ligands gly-pro-arg-pro-amide and gly-his-arg-pro-amide
Structure: Fibrinogen alpha/alpha-e chain. Chain: a, d. Fragment: fragment d (residues 126-191). Engineered: yes. Fibrinogen beta chain. Chain: b, e. Fragment: fragment d (residues 149-461). Engineered: yes. Fibrinogen gamma chain.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: cho cells. Synthetic: yes. Synthetic: yes
Biol. unit: Pentamer (from PQS)
Resolution:
2.80Å     R-factor:   0.212     R-free:   0.270
Authors: M.S.Kostelansky,L.Betts,O.V.Gorkun,S.T.Lord
Key ref:
M.S.Kostelansky et al. (2002). 2.8 A crystal structures of recombinant fibrinogen fragment D with and without two peptide ligands: GHRP binding to the "b" site disrupts its nearby calcium-binding site. Biochemistry, 41, 12124-12132. PubMed id: 12356313 DOI: 10.1021/bi0261894
Date:
20-May-02     Release date:   06-Nov-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P02671  (FIBA_HUMAN) -  Fibrinogen alpha chain from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		866 a.a.
65 a.a.
Protein chains
Pfam   ArchSchema ?
P02675  (FIBB_HUMAN) -  Fibrinogen beta chain from Homo sapiens
Seq:
Struc: 		491 a.a.
298 a.a.
Protein chains
Pfam   ArchSchema ?
P02679  (FIBG_HUMAN) -  Fibrinogen gamma chain from Homo sapiens
Seq:
Struc: 		453 a.a.
299 a.a.
Protein chain
Pfam   ArchSchema ?
P02671  (FIBA_HUMAN) -  Fibrinogen alpha chain from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		866 a.a.
58 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1021/bi0261894 Biochemistry 41:12124-12132 (2002)
PubMed id: 12356313  
 
 
2.8 A crystal structures of recombinant fibrinogen fragment D with and without two peptide ligands: GHRP binding to the "b" site disrupts its nearby calcium-binding site.
M.S.Kostelansky, L.Betts, O.V.Gorkun, S.T.Lord.
 
  ABSTRACT  
 
We report two crystal structures, each at a resolution of 2.8 A, of recombinant human fibrinogen fragment D (rfD) in the absence and presence of peptide ligands. The bound ligands, Gly-Pro-Arg-Pro-amide and Gly-His-Arg-Pro-amide, mimic the interactions of the thrombin exposed polymerization sites, "A" and "B", respectively. This report is the first to describe the structure of fragment D in the presence of both peptide ligands. The structures reveal that recombinant fibrinogen is nearly identical to the plasma protein but with minor changes, like the addition of a proximal fucose to the carbohydrate linked to residue betaGln364, and slightly different relative positions of the beta- and gamma-modules. Of major interest in our structures is that a previously identified calcium site in plasma fibrinogen is absent when Gly-His-Arg-Pro-amide is bound. The peptide-dependent loss of this calcium site may have significant biological implications that are further discussed. These structures provide a foundation for the detailed structural analysis of variant recombinant fibrinogens that were used to identify critical functional residues within fragment D.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19914710 A.S.Soon, S.E.Stabenfeldt, W.E.Brown, and T.H.Barker (2010).
Engineering fibrin matrices: the engagement of polymerization pockets through fibrin knob technology for the delivery and retention of therapeutic proteins.
  Biomaterials, 31, 1944-1954.  
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.  
19650644 S.R.Bowley, N.Okumura, and S.T.Lord (2009).
Impaired protofibril formation in fibrinogen gamma N308K is due to altered D:D and "A:a" interactions.
  Biochemistry, 48, 8656-8663.
PDB code: 3hus
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
18779330 S.Lancellotti, S.Rutella, V.De Filippis, N.Pozzi, B.Rocca, and R.De Cristofaro (2008).
Fibrinogen-elongated {gamma} Chain Inhibits Thrombin-induced Platelet Response, Hindering the Interaction with Different Receptors.
  J Biol Chem, 283, 30193-30204.  
18710925 T.A.Springer, J.Zhu, and T.Xiao (2008).
Structural basis for distinctive recognition of fibrinogen gammaC peptide by the platelet integrin alphaIIbbeta3.
  J Cell Biol, 182, 791-800.
PDB codes: 2vc2 2vdk 2vdl 2vdm 2vdn 2vdo 2vdp 2vdq 2vdr
17090548 A.A.Amelot, M.Tagzirt, G.Ducouret, R.L.Kuen, and B.F.Le Bonniec (2007).
Platelet factor 4 (CXCL4) seals blood clots by altering the structure of fibrin.
  J Biol Chem, 282, 710-720.  
17922803 J.W.Weisel (2007).
Which knobs fit into which holes in fibrin polymerization?
  J Thromb Haemost, 5, 2340-2343.  
16940416 R.I.Litvinov, O.V.Gorkun, D.K.Galanakis, S.Yakovlev, L.Medved, H.Shuman, and J.W.Weisel (2007).
Polymerization of fibrin: Direct observation and quantification of individual B:b knob-hole interactions.
  Blood, 109, 130-138.  
16689770 L.Betts, B.K.Merenbloom, and S.T.Lord (2006).
The structure of fibrinogen fragment D with the 'A' knob peptide GPRVVE.
  J Thromb Haemost, 4, 1139-1141.
PDB code: 2ffd
16838278 M.Sebbag, N.Moinard, I.Auger, C.Clavel, J.Arnaud, L.Nogueira, J.Roudier, and G.Serre (2006).
Epitopes of human fibrin recognized by the rheumatoid arthritis-specific autoantibodies to citrullinated proteins.
  Eur J Immunol, 36, 2250-2263.  
15723073 P.Petzelbauer, P.A.Zacharowski, Y.Miyazaki, P.Friedl, G.Wickenhauser, F.J.Castellino, M.Gröger, K.Wolff, and K.Zacharowski (2005).
The fibrin-derived peptide Bbeta15-42 protects the myocardium against ischemia-reperfusion injury.
  Nat Med, 11, 298-304.  
15998829 R.I.Litvinov, O.V.Gorkun, S.F.Owen, H.Shuman, and J.W.Weisel (2005).
Polymerization of fibrin: specificity, strength, and stability of knob-hole interactions studied at the single-molecule level.
  Blood, 106, 2944-2951.  
12871291 R.F.Doolittle (2003).
X-ray crystallographic studies on fibrinogen and fibrin.
  J Thromb Haemost, 1, 1559-1565.  
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.

 

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