1cu8

Publication Abstract from PubMed

Double rotational-echo double resonance (double REDOR) has been used to investigate the bound conformations of (13)C,(15)N,(19)F-labeled factor Xa inhibitors to bovine trypsin. Carbon-fluorine dipolar couplings were measured by (13)C{(19)F} REDOR with natural-abundance background interferences removed by (13)C{(15)N} REDOR. The conformations of the bound inhibitors were characterized by molecular dynamics (MD) simulations of binding restrained by double REDOR-determined intramolecular C-F distances. A symmetrical bisamidine inhibitor and an asymmetrical monoamidine-monoamine inhibitor of the same general shape had distinctly different conformations in the bound state. According to the MD models, these differences arise from specific interactions of the amidine and amine groups with the active-site residues of trypsin and nearby water molecules.

Conformations of trypsin-bound amidine inhibitors of blood coagulant factor Xa by double REDOR NMR and MD simulations.,McDowell LM, McCarrick MA, Studelska DR, Guilford WJ, Arnaiz D, Dallas JL, Light DR, Whitlow M, Schaefer J J Med Chem. 1999 Sep 23;42(19):3910-8. PMID:10508439^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.