U.S. Department of Health and Human Services

Laboratory of Bioorganic Chemistry

Kenneth A. Jacobson, Ph.D., Chief

​Research Images

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TitleDescriptionImage
Molecular models of four distinct dimeric arrangements of the M3 muscarinic receptorThe structures shown here represent four distinct low-energy M3 muscarinic receptor dimers that are compatible with experimental BRET data (McMillin SM, et al. J. Biol. Chem. 286, 28584-8, 2011).Molecular models of four distinct dimeric arrangements of the M3 muscarinic receptorEnlarge
High-resolution X-ray structure of the M3 muscarinic receptor (M3R)(A) Overall structure of the M3R bound to tiotropium, a muscarinic antagonist used for the treatment of chronic obstructive pulmonary disease and (B) an extracellular view of the tiotropium binding site (Kruse AC, et al. Nature 482, 552-6, 2012).High-resolution X-ray structure of the M3 muscarinic receptor (M3R)Enlarge
Schematic representation of CNO-sensitive designer GPCRs (DREADDs)All depicted DREADDs contain the Y3.33C and A5.46G point mutations in TM3 and TM5, respectively (indicated by the red 'x marks'). The resulting designer receptors are unable to bind acetylcholine (ACh), the endogenous muscarinic receptor agonist, but can be activated by CNO with high potency and efficacy. CNO is a pharmacologically inactive metabolite of clozapine. Depicted are (B) DREADDs differing in their G protein coupling properties (Armbruster BN, et al. Proc. Natl. Acad. Sci. U.S.A. 104, 5163-8, 2007; Guettier JM, et al. Proc. Natl. Acad. Sci. U.S.A. 106, 19197-19202, 2009) and (C) the structure of an arrestin-biased DREADD (Nakajima KI and Wess J. Mol. Pharmacol. 82, 575-82, 2012).Schematic representation of CNO-sensitive designer GPCRs (DREADDs)Enlarge
Wess Photo Lab Members(From left to right): Kelly Hu, Yinghong Cui, Derek Bone, Sally McMillin, Shalini Jain, Jürgen Wess, Mario Rossi, Ken-ichiro Nakajima, Wataru Sakamoto, and Jianxin HuWess Photo Lab MembersEnlarge
Hexasaccharide conjugate (Hexa-rTT-Hc)Conjugate construct (vaccine) made from the Antigen and Carrier by squaric acid chemistry of conjugation, utilizing the sole amino group in the Spacer and amino group in the L-lysine residues present in the carrier.Hexasaccharide conjugate (Hexa-rTT-Hc)Enlarge