1BBR

THE STRUCTURE OF RESIDUES 7-16 OF THE A ALPHA CHAIN OF HUMAN FIBRINOGEN BOUND TO BOVINE THROMBIN AT 2.3 ANGSTROMS RESOLUTION

Summary for 1BBR

• Entry DOI: 10.2210/pdb1bbr/pdb
• Descriptor: EPSILON-THROMBIN, FIBRINOGEN ALPHA/ALPHA-E CHAIN PRECURSOR, ... (6 entities in total)
• Functional Keywords: serine protease
• Biological source: Bos taurus (cattle); More
• Cellular location: Secreted, extracellular space: P00735 P00735 P00735 P00735; Secreted: P02671
• Total number of polymer chains: 10
• Total formula weight: 109682.41

Authors

Martin, P.,Edwards, B. (deposition date: 1992-04-27, release date: 1994-01-31, Last modification date: 2024-10-30)

Primary citation

Martin, P.D.,Robertson, W.,Turk, D.,Huber, R.,Bode, W.,Edwards, B.F.
The structure of residues 7-16 of the A alpha-chain of human fibrinogen bound to bovine thrombin at 2.3-A resolution.
J.Biol.Chem., 267:7911-7920, 1992

PubMed Abstract: The tetradecapeptide Ac-D-F-L-A-E-G-G-G-V-R-G-P-R-V-OMe, which mimics residues 7f-20f of the A alpha-chain of human fibrinogen, has been co-crystallized with bovine thrombin from ammonium sulfate solutions in space group P2(1) with unit cell dimensions of a = 83.0 A, b = 89.4 A, c = 99.3 A, and beta = 106.6 degrees. Three crystallographically independent complexes were located in the asymmetric unit by molecular replacement using the native bovine thrombin structure as a model. The standard crystallographic R-factor is 0.167 at 2.3-A resolution. Excellent electron density could be traced for the decapeptide, beginning with Asp-7f and ending with Arg-16f in the active site of thrombin; the remaining 4 residues, which have been cleaved from the tetradecapeptide at the Arg-16f/Gly-17f bond, are not seen. Residues 7f-11f at the NH2 terminus of the peptide form a single turn of alpha-helix that is connected by Gly-12f, which has a positive phi angle, to an extended chain containing residues 13f-16f. The major specific interactions between the peptide and thrombin are 1) a hydrophobic cage formed by residues Tyr-60A, Trp-60D, Leu-99, Ile-174, Trp-215, Leu-9f, Gly-13f, and Val-15f that surrounds Phe-8f; 2) a hydrogen bond linking Phe-8f NH to Lys-97 O;3) a salt link between Glu-11f and Arg-173; 4) two antiparallel beta-sheet hydrogen bonds between Gly-14f and Gly-216; and 5) the insertion of Arg-16f into the specificity pocket. Binding of the peptide is accompanied by a considerable shift in two of the loops near the active site relative to human D-phenyl-L-prolyl-L-arginyl chloromethyl ketone (PPACK)-thrombin.

PubMed: 1560020

Experimental method

X-RAY DIFFRACTION (2.3 Å)