HIGH-RESOLUTION CRYSTAL-STRUCTURES OF RECOMBINANT HUMAN RENIN IN COMPLEX WITH POLYHYDROXYMONOAMIDE INHIBITORS

The crystal structures of recombinant glycosylated human renin in comp lex with several polyhydroxymonoamide inhibitors have been determined at up to 1.8 Angstrom resolution. The high resolution structures permi t a detailed analysis of the conformation of renin, the interactions b etween the inhibitors and renin, and the network of ordered water mole cules. The polyhydroxymonoamide inhibitors are bound with their backbo nes in an extended conformation, and with their side-chains occupying the S-3 to S-1. pockets. The inhibited renin molecules are shown to ex ist in both the closed and the open conformations. Inhibitors bound to the two distinct forms of renin can assume different conformations at the P-3 position.