5PGW

CRYSTAL STRUCTURE OF 11BETA-HSD1 DOUBLE MUTANT (L262R, F278E) COMPLEXED WITH 2-[(1R,3S,5R,7S)-2-[4-(4-FLUOROPHENYL)PHENYL]-6-HYDROXYADAMANTAN-2-YL]-1-(3- HYDROXYAZETIDIN-1-YL)ETHAN-1-ONE

Summary for 5PGW

• Entry DOI: 10.2210/pdb5pgw/pdb
• Group deposition: 11betaHSD1 (G_1002017)
• Descriptor: Corticosteroid 11-beta-dehydrogenase isozyme 1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 2-[(1R,3S,5R,7S)-2-[4-(4-FLUOROPHENYL)PHENYL]-6-HYDROXYADAMANTAN-2-YL]-1-(3-HYDROXYAZETIDIN-1-YL)ETHAN-1-ONE, ... (4 entities in total)
• Functional Keywords: 11b-hsd1, sdr, dehydrogenase, hydroxysteroid, inhibitor, oxidoreductase-oxidoreductase inhibi complex, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Endoplasmic reticulum membrane ; Single-pass type II membrane protein : P28845
• Total number of polymer chains: 4
• Total formula weight: 130101.13

Authors

Sheriff, S. (deposition date: 2017-02-06, release date: 2017-11-01, Last modification date: 2024-03-06)

• Primary citation: Ye, X.Y.,Chen, S.Y.,Wu, S.,Yoon, D.S.,Wang, H.,Hong, Z.,O'Connor, S.P.,Li, J.,Li, J.J.,Kennedy, L.J.,Walker, S.J.,Nayeem, A.,Sheriff, S.,Camac, D.M.,Ramamurthy, V.,Morin, P.E.,Zebo, R.,Taylor, J.R.,Morgan, N.N.,Ponticiello, R.P.,Harrity, T.,Apedo, A.,Golla, R.,Seethala, R.,Wang, M.,Harper, T.W.,Sleczka, B.G.,He, B.,Kirby, M.,Leahy, D.K.,Li, J.,Hanson, R.L.,Guo, Z.,Li, Y.X.,DiMarco, J.D.,Scaringe, R.,Maxwell, B.,Moulin, F.,Barrish, J.C.,Gordon, D.A.,Robl, J.A.; Discovery of Clinical Candidate 2-((2S,6S)-2-Phenyl-6-hydroxyadamantan-2-yl)-1-(3'-hydroxyazetidin-1-yl)ethanone [BMS-816336], an Orally Active Novel Selective 11 beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitor.; J. Med. Chem., 60:4932-4948, 2017; PubMed: 28537398; DOI: 10.1021/acs.jmedchem.7b00211

Experimental method

X-RAY DIFFRACTION (2.37 Å)