Secondary structure and signal assignments of human-immunodeficiency-virus-1 protease complexed to a novel, structure-based inhibitor.

We report comprehensive NMR studies in solution of the human-immunodeficiency-virus (HIV)-1 protease. Stable solutions of the protease were obtained by complexing the protein to a designed cyclic urea inhibitor DMP 323. A variety of triple-resonance experiments provided essentially complete 1H, 13C and 15N NMR signal assignments of the protease. These assignments, together with short-range NOE constraints, coupling constants and hydrogen-exchange data, yielded the secondary structure of the protease in solution. The results reported herein open the way to the determination of the high-resolution three-dimensional solution structures of protease/inhibitor complexes, as well as to studies of protease dynamics and solvent interactions.