Unexpected binding mode of a cyclic sulfamide HIV-1 protease inhibitor.
Two cyclic, C2-symmetric HIV-1 protease inhibitors, one sulfamide and one urea derivative, both comprising phenyl ether groups in the P1/P1' positions, were cocrystallized with HIV-1 protease, and the crystal structures were determined to 2.0 A resolution. The structure of the urea 2 showed a conformation similar to that reported for the related urea 3 by Lam et al., while the sulfamide 1 adopted an unanticipated conformation in which the P1' and P2' side chains were transposed.
Bäckbro
K
K
Department of Molecular Biology, Uppsala University, Sweden.
Löwgren
S
S
Osterlund
K
K
Atepo
J
J
Unge
T
T
Hultén
J
J
Bonham
N M
NM
Schaal
W
W
Karlén
A
A
Hallberg
A
A
D001381:Azepines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011485:Protein Binding; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
C105324:1,3-dibenzyl-5,6--dihydroxy-4,7-di-(phenoxymethyl)-1,3-azepin-2-one; C105323:1,3-dibenzyl-5,6-dihydroxy-4,7-di-(phenoxymethyl)-2-thia-1,3-azepine S,S-dioxide; D001381:Azepines; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D016333:HIV Protease