Protease/DMP-323 complex

HIV-protease/inhibitor complexes have a molecular weight of approximately 22 kDa. Although NMR spectroscopy is well suited to determination of the structure of molecules in this size range, efforts to determine the solution structure of the complex were hampered by the fact that the protease undergoes rapid autocatalysis in solution. It required the development of potent inhibitors before NMR studies of the complex became feasible. The first solution structure of HIV-protease bound to the cyclic urea inhibitor DMP-323 (Fig. 25) was reported by Yamazaki in 1996.133 The protease exists as a homodimer. Each 99-residue monomer contains ten /3-strands and the dimer is stabilized by a four-stranded antiparallel /3-sheet formed by the N- and C-terminal strands of each monomer. The active site of the enzyme is formed at the interface, where each monomer contributes a catalytic triad (Asp25-Thr26-Gly27) that is... 

---