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PDBsum entry 2oyi

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protein ligands metals Protein-protein interface(s) links
Blood clotting PDB id
2oyi
Jmol
Contents
Protein chains
65 a.a. *
301 a.a. *
299 a.a. *
56 a.a. *
Ligands
GLY-PRO-ARG-PRO ×4
NAG-NAG-FUC ×2
Metals
_CA ×4
Waters ×150
* Residue conservation analysis
PDB id:
2oyi
Name: Blood clotting
Title: Crystal structure of fragment d of gammad298,301a fibrinogen peptide ligand gly-pro-arg-pro-amide
Structure: Fibrinogen alpha chain. Chain: a, d. Fragment: residues 126-191. Engineered: yes. Fibrinogen beta chain. Chain: b, e. Fragment: residues 149-461. Engineered: yes. Fibrinogen gamma chain.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: fga. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Gene: fgb. Gene: fgg. Synthetic: yes.
Resolution:
2.70Å     R-factor:   0.216     R-free:   0.256
Authors: M.S.Kostelansky,O.V.Gorkun,S.T.Lord
Key ref: M.S.Kostelansky et al. (2007). Probing the gamma2 calcium-binding site: studies with gammaD298,301A fibrinogen reveal changes in the gamma294-301 loop that alter the integrity of the "a" polymerization site. Biochemistry, 46, 5114-5123. PubMed id: 17411074 DOI: 10.1021/bi602607a
Date:
22-Feb-07     Release date:   15-May-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P02671  (FIBA_HUMAN) -  Fibrinogen alpha chain
Seq:
Struc:
 
Seq:
Struc:
866 a.a.
65 a.a.
Protein chains
Pfam   ArchSchema ?
P02675  (FIBB_HUMAN) -  Fibrinogen beta chain
Seq:
Struc:
491 a.a.
301 a.a.
Protein chains
Pfam   ArchSchema ?
P02679  (FIBG_HUMAN) -  Fibrinogen gamma chain
Seq:
Struc:
453 a.a.
299 a.a.*
Protein chain
Pfam   ArchSchema ?
P02671  (FIBA_HUMAN) -  Fibrinogen alpha chain
Seq:
Struc:
 
Seq:
Struc:
866 a.a.
56 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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  

 

 
DOI no: 10.1021/bi602607a Biochemistry 46:5114-5123 (2007)
PubMed id: 17411074  
 
 
Probing the gamma2 calcium-binding site: studies with gammaD298,301A fibrinogen reveal changes in the gamma294-301 loop that alter the integrity of the "a" polymerization site.
M.S.Kostelansky, K.C.Lounes, L.F.Ping, S.K.Dickerson, O.V.Gorkun, S.T.Lord.
 
  ABSTRACT  
 
To determine the significance of the gamma2 calcium-binding site in fibrin polymerization, we synthesized the fibrinogen variant, gammaD298,301A. We expected these two alanine substitutions to prevent calcium binding in the gamma2 site. We examined the influence of calcium on the polymerization of gammaD298,301A fibrinogen, evaluated its plasmin susceptibility, and solved 2.7 and 2.4 A crystal structures of the variant with the peptide ligands Gly-Pro-Arg-Pro-amide (GPRP) and Gly-His-Arg-Pro-amide (GHRP), respectively. We found that thrombin-catalyzed polymerization of gammaD298,301A fibrinogen was modestly impaired, whereas batroxobin-catalyzed polymerization was significantly impaired relative to normal fibrinogen. Notably, the influence of calcium on polymerization was the same for the variant and for normal fibrinogen. Fibrinogen gammaD298,301A was more susceptible to plasmin proteolysis in the presence of GPRP. This finding suggests structural changes in the near-by "a" polymerization site. Comparisons of the structures revealed minor conformational changes in the gamma294-301 loop that are likely responsible for the weakened "a" site. When considered altogether, the data suggest that the gamma2 calcium-binding site does not significantly modulate polymerization. We cannot, however, rule out the possibility that the weakened "a" polymerization site masks an important role for the gamma2 calcium-binding site in normal polymerization. Somewhat unexpectedly, the structure data showed that GPRP bound to the "b" site and induced the same local conformational changes as GHRP to this site. This structure shows that "A:b" interactions can occur and suggests that these may participate in normal polymerization.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
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.