1LTJ

Crystal Structure of Recombinant Human Fibrinogen Fragment D with the Peptide Ligands Gly-Pro-Arg-Pro-Amide and Gly-His-Arg-Pro-Amide

Summary for 1LTJ

• Entry DOI: 10.2210/pdb1ltj/pdb
• Related: 1FZA 1FZB 1FZC 1FZE 1FZF 1FZG 1LT9
• Descriptor: Fibrinogen alpha/alpha-E chain, Fibrinogen Beta chain, Fibrinogen Gamma chain, ... (8 entities in total)
• Functional Keywords: blood coagulation, fibrinogen, fibrinogen fragment d, recombinant fibrinogen fragment d, recombinant fibrinogen, recombinant fibrinogen fragment d with two peptide ligands, blood clotting
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 160899.89

Authors

Kostelansky, M.S.,Betts, L.,Gorkun, O.V.,Lord, S.T. (deposition date: 2002-05-20, release date: 2002-11-06, Last modification date: 2024-10-09)

Primary citation

Kostelansky, M.S.,Betts, L.,Gorkun, O.V.,Lord, S.T.
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, 2002

PubMed 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.

PubMed: 12356313
DOI: 10.1021/bi0261894

Experimental method

X-RAY DIFFRACTION (2.8 Å)