Crystallographic evidence that the F2 kringle catalytic domain linker of prothrombin does not cover the fibrinogen recognition exosite.
The 2.6-A x-ray crystal structure of bovine alpha-thrombin in complex with rhodniin, a protein inhibitor isolated from the bug Rhodnius prolixus, has been solved and refined. The structure has enabled us to trace the N-terminal part of the 49-residue A-chain of bovine alpha-thrombin for the first time, which is fixed in a U-shaped loop on the molecular surface opposite the active site canyon. Model building shows that the 25 amino acid residues that link the A-chain and F2 kringle cannot run through the fibrinogen recognition exosite. This demonstrates that this fibrinogen recognition exosite is available in prothrombin and meizothrombin.
van de Locht
A
A
Department of Structural Research, Max Planck Institute for Biochemistry, D-82152 Martinsried, Germany.
Stubbs
M T
MT
Bauer
M
M
Bode
W
W
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D018360:Crystallography, X-Ray; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007301:Insect Hormones / Q000378:metabolism; D019476:Insect Proteins; D018082:Kringles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011516:Prothrombin / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D014714:Vertebrates
D007301:Insect Hormones; D019476:Insect Proteins; D015842:Serine Proteinase Inhibitors; C082506:rhodniin protein, Rhodnius; D011516:Prothrombin; D005340:Fibrinogen