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

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Abstract
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.