HIV-1 PROTEASE COMPLEXED WITH A CYCLIC PHE-ILE-VAL PEPTIDOMIMETIC INHIBITOR
[1-BENZYL-3-(8-SEC-BUTYL-7,10-DIOXO-2-OXA-6,9-DIAZA-BICYCLO[11.2.2] HEPTADECA-1(16),13(17),14-TRIEN-11-YLAMINO)-2-HYDROXY-PROPYL]-CARBAMIC ACID TERT-BUTYL ESTER
Substrate-based cyclic peptidomimetics of Phe-Ile-Val that inhibit HIV-1 protease using a novel enzyme-binding mode.
PQITLWKRPLVTIRIGGQLKEALLDTGADDTVIEEMNLPGKWKPKMIGGIGGFIKVRQYDQIPVEI(ABA)GHKAIGTVL VGPTPVNIIGRNLLTQIG(ABA)TLNF
PQITLWKRPLVTIRIGGQLKEALLDTGADDTVIEEMNLPGKWKPKMIGGIGGFIKVRQYDQIPVEIAGHKAIGTVLVGPT PVNIIGRNLLTQIGATLNF
GLN 7 WAS REPLACED BY LYS TO PREVENT AUTOCLEAVAGE. LEU 33 WAS REPLACED BY ILE TO PREVENT AUTOCLEAVAGE. CYS 67 WAS REPLACED BY ABA FOR EASE OF CHEMICAL SYNTHESIS. CYS 95 WAS REPLACED BY ABA FOR EASE OF CHEMICAL SYNTHESIS.
tert-butyl [(1S,2S)-1-benzyl-2-hydroxy-3-{[(8S,11R)-8-[(1R)-1-methylpropyl]-7,10-dioxo-2-oxa-6,9-diazabicyclo[11.2.2]heptadeca-1(15),13,16-trien-11-yl]amino}propyl]carbamate
RESIDUES 50 AND 51 IN THE FLAP REGION OF BOTH SUBUNITS ARE DISORDERED AND WERE MODELLED IN TWO CONFORMATIONS. HOWEVER, THESE REGIONS OF THE STRUCTURE HAVE RELATIVELY POOR GEOMETRY.
ASPARTYL PROTEINASE, AIDS, ASPARTYL PROTEASE, HYDROLASE-HYDROLASE INHIBITOR complex
FFREDLAFLQGKAREFSSEQTRANSPTRRELQVWGGENNSLSEAGADRQGTVSFNFPQITLWQRPLVTIRIGGQLKEALL DTGADDTVLEEMNLPGKWKPKMIGGIGGFIKVRQYDQIPVEICGHKAIGTVLVGPTPVNIIGRNLLTQIGCTLNFPISPI ETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPVFAIKKKDSTKWRKLVDFRELNKRTQ DFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDKDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMT KILEPFRKQNPDIVIYQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGFTTPDKKHQKEPPFLWMGYELHPDKWTVQPIM LPEKDSWTVNDIQKLVGKLNWASQIYAGIKVKQLCKLLRGTKALTEVIPLTEEAELELAENREILKEPVHEVYYDPSKDL VAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGAHTNDVKQLTEAVQKVSTESIVIWGKIPKFKLPIQKETWEAWWMEY WQATWIPEWEFVNTPPLVKLWYQLEKEPIVGAETFYVDGAANRETKLGKAGYVTDRGRQKVVSIADTTNQKTELQAIHLA LQDSGLEVNIVTDSQYALGIIQAQPDKSESELVSQIIEQLIKKEKVYLAWVPAHKGIGGNEQVDKLVSAGIRKVLFLNGI DKAQEEHEKYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKIILVAVHVASGYIE AEVIPAETGQETAYFLLKLAGRWPVKTIHTDNGSNFTSTTVKAACWWAGIKQEFGIPYNPQSQGVVESMNNELKKIIGQV RDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQNFRVYYRDNKDPLWKGPAKLLWKG EGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVASRQDED