High resolution crystal structures of recombinant human renin in complex with polyhydroxymonoamide inhibitors.
The crystal structures of recombinant glycosylated human renin in complex with several polyhydroxymonoamide inhibitors have been determined at up to 1.8 A resolution. The high resolution structures permit a detailed analysis of the conformation of renin, the interactions between the inhibitors and renin, and the network of ordered water molecules. The polyhydroxymonoamide inhibitors are bound with their backbones in an extended conformation, and with their side-chains occupying the S3 to S1 pockets. The inhibited renin molecules are shown to exist in both the closed and the open conformations. Inhibitors bound to the two distinct forms of renin can assume different conformations at the P3 position.
Tong
L
L
Department of Inflammatory Diseases, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877, USA.
Pav
S
S
Lamarre
D
D
Pilote
L
L
LaPlante
S
S
Anderson
P C
PC
Jung
G
G
D000577:Amides / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012083:Renin / Q000737:chemistry* / Q000378:metabolism; D014867:Water / Q000737:chemistry; D000092502:Renin Inhibitors
D000577:Amides; D011994:Recombinant Proteins; D012083:Renin; D014867:Water; D000092502:Renin Inhibitors