1bbr
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THE STRUCTURE OF RESIDUES 7-16 OF THE A ALPHA CHAIN OF HUMAN FIBRINOGEN BOUND TO BOVINE THROMBIN AT 2.3 ANGSTROMS RESOLUTION
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Afibrinogenemia, congenital OMIM:[134820], Amyloidosis, hereditary renal OMIM:[134820], Dysfibrinogenemia, alpha type, causing bleeding diathesis OMIM:[134820], Dysfibrinogenemia, alpha type, causing recurrent thrombosis OMIM:[134820]
About this StructureAbout this Structure
1BBR is a Protein complex structure of sequences from Bos taurus and Homo sapiens with ACE as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
ReferenceReference
The structure of residues 7-16 of the A alpha-chain of human fibrinogen bound to bovine thrombin at 2.3-A resolution., Martin PD, Robertson W, Turk D, Huber R, Bode W, Edwards BF, J Biol Chem. 1992 Apr 15;267(11):7911-20. PMID:1560020
Page seeded by OCA on Mon Nov 12 16:08:11 2007