High-resolution NMR studies of fibrinogen-like peptides in solution: Interaction of thrombin with residues 1-23 of the A. alpha. chain of human fibrinogen
- Cornell Univ., Ithaca, NY (USA)
The interaction of the following human fibrinogen-like peptides with bovine thrombin was studied by use of one- and two-dimensional NMR techniques in aqueous solution: Ala(1)-Asp-Ser-Gly-Glu-Gly-Asp-Phe(8)-Leu-Ala-Glu-Gly-Gly-Gly-Val-Arg(16)-Gly(17)-Pro-Arg(19)-Val(20)-Val-Glu-Arg (F10), residues 1-16 of F10 (fibrinopeptide A), residues 17-23 of F10 (F12), residues 1-20 of F10 (F13), residues 6-20 of F10 with Arg(16) replaces by a Gly residue (F14), and residues 6-19 of F10 with Arg(16) replaced by a Leu residue (F15). At pH 5.3 and 25{degree}C, the Arg(16)-Gly(17) peptide bonds of both peptides F10 and F13 were cleaved instantaneously in the presence of 0.6 mM thrombin, whereas the cleavage of the Arg(19)-Val(20) peptide bonds in peptides F12, F13, and F14 took over 1 h for completion. On the basis of observations of line broadening, fibrinopeptide A was found to bind to thrombin. While resonances from residues Ala(1)-Glu(5) were little affected, binding of fibrinopeptide A to thrombin caused significant line broadening of NH and side-chain proton resonances within residues Asp(7)-Arg(16). Peptides with Arg(16) replaced by Gly and Leu, respectively, i.e.; F14 and F15, were also found to bind to thrombin but with a different conformation, as indicated by the absence of the long-range NOEs observed with fibrinopeptide A. Residues Asp(7)-Arg(16) constitute an essential structural element in the interaction of thrombin with fibrinogen.
- OSTI ID:
- 5671941
- Journal Information:
- Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 28:7; ISSN 0006-2960; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
AQUEOUS SOLUTIONS
BLOOD COAGULATION FACTORS
CATTLE
CHEMICAL REACTIONS
COAGULANTS
CROSS-LINKING
DISPERSIONS
DOMESTIC ANIMALS
DRUGS
ENZYMES
FIBRINOGEN
GLOBULINS
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROLASES
MAGNETIC RESONANCE
MAMMALS
MAN
MIXTURES
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PEPTIDES
PH VALUE
POLYMERIZATION
PRIMATES
PROTEINS
PURIFICATION
RESONANCE
RUMINANTS
SERINE PROTEINASES
SOLUTIONS
SPECTRA
THROMBIN
VERTEBRATES