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-immunodef iciency-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 essential ly complete H-1, C-13 and N-15 NMR signal assignments of the protease. These assignments, together with short-range NOE constraints, couplin g constants and hydrogen-exchange data, yielded the secondary structur e of the protease in solution. The results reported herein open the wa y to the determination of the high-resolution three-dimensional soluti on structures of protease/inhibitor complexes, as well as to studies o f protease dynamics and solvent interactions.