PMID: 18467335

 

    Legend: Gene, Sites

Title : N-glycans and the N terminus of protein C inhibitor affect the cofactor-enhanced rates of thrombin inhibition

Abstract :
  1. Protein C inhibitor ( PCI ) is a serine protease inhibitor, displaying broad protease specificity, found in blood and other tissues
  2. In blood, it is capable of inhibiting both procoagulant and anticoagulant proteases
  3. Mechanisms that provide specificity to PCI remain largely unrevealed
  4. In this study we have for the first time provided a full explanation for the marked size heterogeneity of blood-derived PCI and identified functional differences between naturally occurring PCI variants
  5. The heterogeneity was caused by differences in N-glycan structures, N-glycosylation occupancy, and the presence of a Delta6-N-cleaved form
  6. Bi-, tri-, and tetra-antennary complex N-glycans were identified
  7. Fucose residues were identified both on the core GlcNAc and as parts of sialyl-Le(a/x) epitopes
  8. Moreover, a glycan with a com position that implied a di-sialyl antenna was observed
  9. PCI was N-glycosylated at all three potential N-glycosylation sites, Asn-230, Asn-243, and Asn-319 , but a small fraction of PCI lacked the N-glycan at Asn-243
  10. The overall removal of N-glycans affected the maximal heparin- and thrombomodulin-enhanced rates of thrombin inhibition differently in different solution conditions
  11. In contrast, the Delta6-N-region increased both the heparin- and the thrombomodulin-enhanced rates of thrombin inhibition at all conditions examined
  12. These results thus demonstrate that the N-linked glycans and the N-terminal region of blood-derived PCI in different ways affect the cofactor-enhanced rates of thrombin inhibition and provide information on the mechanisms by which this may be achieved
  13. The findings are medically important, in view of the documented association of PCI with atherosclerotic plaques and the promising effect of PCI on reducing hypercoagulability states
Output (sent_index, trigger, protein, sugar, site):
  • 0. inhibitor, , protein C inhibitor, N-glycans, -
  • 12. PCI, , PCI, the N-linked glycans, -
  • 4. heterogeneity, , PCI, -, -
  • 7. epitopes, , -, Fucose residues, epitopes
  • 9. N-glycosylated, , -, -, Asn-230, Asn-243, and Asn-319
  • 9. N-glycosylated, , PCI, -, Asn-230, Asn-243, and Asn-319
  • 9. N-glycosylation, , -, -, Asn-230, Asn-243, and Asn-319
  • 9. PCI, , PCI, a small fraction, -
Output(Part-Of) (sent_index, protein, site):
  • 0. protein C inhibitor, terminus
  • 12. PCI, region
*Output_Site_Fusion* (sent_index, protein, sugar, site):
  • 9. PCI, -, Asn-230, Asn-243, and Asn-319

 

 

Protein NCBI ID SENTENCE INDEX