title: Unexpected binding mode of a cyclic sulfamide HIV-1 protease inhibitor.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Uppsala University, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Bäckbro
authors.forename: S
authors.initials: S
authors.lastname: Löwgren
authors.forename: K
authors.initials: K
authors.lastname: Osterlund
authors.forename: J
authors.initials: J
authors.lastname: Atepo
authors.forename: T
authors.initials: T
authors.lastname: Unge
authors.forename: J
authors.initials: J
authors.lastname: Hultén
authors.forename: N M
authors.initials: NM
authors.lastname: Bonham
authors.forename: W
authors.initials: W
authors.lastname: Schaal
authors.forename: A
authors.initials: A
authors.lastname: Karlén
authors.forename: A
authors.initials: A
authors.lastname: Hallberg
mesh_terms: 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
chemical_list: 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