Crystal structures of inhibitor complexes of M‐PMV protease with visible flap loops

Abstract

Mason-Pfizer monkey virus protease (PR) was crystallized in complex with two pepstatin-based inhibitors in P1 space group. In both crystal structures, the extended flap loops that lock the inhibitor/substrate over the active site, are visible in the electron density either completely or with only small gaps, providing the first observation of the conformation of the flap loops in dimeric complex form of this retropepsin. The H-bond network in the active site (with D26N mutation) differs from that reported for the P2 1 crystal structures and is similar to a rarely occurring system in HIV-1 PR.

Precursors of Viral Proteases as Distinct Drug Targets

“…In general, partially processed and unprocessed peptides of amino acid sequences found adjacent to the protease region might influence the protease domain, thus affecting its dimerization ability [ 109 , 110 ], substrate specificity, accessibility of cleavage sites, structural features, and stability. Among other retroviruses, as many as three C-terminally truncated mature forms of Mason–Pfizer monkey virus (M-PMV) protease were reported to exist and these have different levels of activity and stability [ 111 , 112 , 113 , 114 , 115 ].…”