1ltj
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Crystal Structure of Recombinant Human Fibrinogen Fragment D with the Peptide Ligands Gly-Pro-Arg-Pro-Amide and Gly-His-Arg-Pro-Amide
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Afibrinogenemia, congenital OMIM:[134820], Afibrinogenemia, congenital OMIM:[134830], Amyloidosis, hereditary renal OMIM:[134820], Dysfibrinogenemia, alpha type, causing bleeding diathesis OMIM:[134820], Dysfibrinogenemia, alpha type, causing recurrent thrombosis OMIM:[134820], Dysfibrinogenemia, beta type OMIM:[134830], Dysfibrinogenemia, gamma type OMIM:[134850], Hypofibrinogenemia, gamma type OMIM:[134850], Thrombophilia, dysfibrinogenemic OMIM:[134830], Thrombophilia, dysfibrinogenemic OMIM:[134850]
About this StructureAbout this Structure
1LTJ is a Protein complex structure of sequences from Homo sapiens with CA as ligand. Full crystallographic information is available from OCA.
ReferenceReference
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., Kostelansky MS, Betts L, Gorkun OV, Lord ST, Biochemistry. 2002 Oct 8;41(40):12124-32. PMID:12356313
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