Tao Che | The Che Lab | Washington University in St. Louis

Ligand and G-protein selectivity in kappa opioid receptor

Han JM, Zhang JY, Nazarova AL, Bernhard SM, Krumm BE, Zhao L, Lam JH, Rangari VA, Majumdar S, Nichols DE, Katritch V, Yuan P, Fay JF#, Che T#. Nature. 2023. PMID: 37138078.

Molecular mechanism of biased signaling at the kappa opioid receptor

El Daibani A*, Paggi JM*, Kim K*, Laloudakis YD*, Popov P, Bernhard SM, Krumm BE, Olsen RHJ, Diberto J, Carroll FI, Katritch V, Wünsch B, Dror RO#, Che T#. Nat Commun. 2023. PMID: 36906681.

5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology

Peng Y*, McCorvy JD*, Harpsøe K*, Lansu K, Yuan S, Popov P, Qu L, Pu M, Che T, Nikolajsen LF, Huang XP, Wu Y, Shen L, Bjørn-Yoshimoto WE, Ding K, Wacker D, Han GW, Cheng J, Katritch V, Jensen AA, Hanson MA, Zhao S, Gloriam DE, Roth BL, Stevens RC, Liu ZJ. Cell. 2018; PMID: 29398112.

A Novel Mitragynine Analog with Low-Efficacy Mu Opioid Receptor Agonism Displays Antinociception with Attenuated Adverse Effects

Chakraborty S, DiBerto JF, Faouzi A, Bernhard SM, Gutridge AM, Ramsey S, Zhou Y, Provasi D, Nuthikattu N, Jilakara R, Nelson MNF, Asher WB, Eans SO, Wilson LL, Chintala SM, Filizola M, van Rijn RM, Margolis EB, Roth BL, McLaughlin JP, Che T, Sames D, Javitch JA, Majumdar S. J Med Chem. 2021. PMID: 34505767.

A promising chemical series of positive allosteric modulators of the μ-opioid receptor that enhance the antinociceptive efficacy of opioids but not their adverse effects

Pryce KD, Kang HJ, Sakloth F, Liu Y, Khan S, Toth K, Kapoor A, Nicolais A, Che T, Qin L, Bertherat F, Kaniskan HÜ, Jin J, Cameron MD, Roth BL, Zachariou V, Filizola M. Neuropharmacology. 2021. PMID: 34153316.

Analysis of carotenoid isomerase activity in a prototypical carotenoid cleavage enzyme, apocarotenoid oxygenase (ACO)

Sui X, Kiser PD, Che T, Carey PR, Golczak M, Shi W, von Lintig J, Palczewski K. J Biol Chem. 2014; 289(18):12286-99. PMID: 4007427.

Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity

Kaplan AL, Confair DN, Kim K, Barros-Alvarez X, Rodriguiz RM, Yang Y, Kweon OS, Che T, McCorvy JD, Kamber DN, Phelan JP, Martins LC, Pogorelov VM, DiBerto JF, Slocum ST, Huang XP, Kumar JM, Robertson MJ, Panova O, Seven AB, Wetsel AQ, Wetsel WC, Irwin JJ, Skiniotis G, Shoichet BK, Roth BL, Ellman JA. Nature. 2022 PMID: 36171289.

beta-Lactamase inhibition by 7-alkylidenecephalosporin sulfones: allylic transposition and formation of an unprecedented stabilized acyl-enzyme

Rodkey EA, McLeod DC, Bethel CR, Smith KM, Xu Y, Chai W, Che T, Carey PR, Bonomo RA, van den Akker F, Buynak JD. J Am Chem Soc. 2013; 135(49):18358-69. PMID: 4042847.

Biased ligands at opioid receptors: Current status and future directions

Che T#, Dwivedi-Agnihotri H, Shukla AK, Roth BL#. Science Signaling. 2021. PMID: 33824179.

Capturing receptor states with glue

Bernhard SM & Che T. Nat Chem Biol. 2023. PMID: 37580553

Carboxylation and decarboxylation of active site Lys 84 controls the activity of OXA-24 beta-lactamase of Acinetobacter baumannii: Raman crystallographic and solution evidence

Che T, Bonomo RA, Shanmugam S, Bethel CR, Pusztai-Carey M, Buynak JD, Carey PR. J Am Chem Soc. 2012; 134(27):11206-15. PMID: 3404726.

Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site

Uprety R*, Che T*, Zaidi SA*, Grinnell SG, Varga BR, Faouzi A, Slocum ST, Allaoa A, Varadi A, Nelson M, Bernhard SM, Kulko E, Le Rouzic V, Eans S, Simons CA, Hunkele A, Subrath J, Pan YX, Javitch JA, McLaughlin JP, Roth BL#, Pasternak GW, Katritch V#, Majumdar S#. eLife. 2021. PMID: 33555255.

Crystal Structure of an LSD-Bound Human Serotonin Receptor

Wacker D, Wang S, McCorvy JD, Betz RM, Venkatakrishnan AJ, Levit A, Lansu K, Schools ZL, Che T, Nichols DE, Shoichet BK, Dror RO, Roth BL. Cell. 2017; 168(3):377-389. PMID: 28129538. (Journal Cover)

D4 dopamine receptor high-resolution structures enable the discovery of selective agonists

Wang S*, Wacker D*, Levit A*, Che T, Betz RM, McCorvy JD, Venkatakrishnan AJ, Huang XP, Dror RO, Shoichet BK, Roth BL. Science. 2017; 358(6361):381-386. PMID: 29051383.

Design and structural validation of peptide-drug conjugate ligands of the kappa-opioid receptor.

Muratspahić E*, Deibler K*, Han J*, Tomašević N, Jadhav KB, Olivé-Marti AL, Hochrainer N, Hellinger R, Koehbach J, Fay JF, Rahman MH, Hegazy L, Craven TW, Varga BR, Bhardwaj G, Appourchaux K, Majumdar S, Muttenthaler M, Hosseinzadeh P, Craik DJ, Spetea M, Che T#, Baker D#, Gruber CW#. Nat Commun. 2023. PMID: 38052802.

Detecting a quasi-stable imine species on the Reaction Pathway of SHV-1 β-Lactamase and 6β-(Hydroxymethyl)penicillanic Acid Sulfones

Che T, Rodkey EA, Bethel CR, Shanmugam S, Ding Z, Pusztai-Carey M, Nottingham M, Chai W, Buynak JD, Bonomo RA, van den Akker F, Carey PR. Biochemistry. 2015; 54(3):734-43. PMID: 25536850.

Development of Novel Quinoxaline-Based Kappa-Opioid Receptor Agonists for the Treatment of Neuroinflammation

Tangherlini G, Kalinin DV, Schepmann D, Che T, Mykicki N, Ständer S, Loser K, Wünsch B. J Med Chem. 2019. PMID: 30543421.

Discrepancies in kappa opioid agonist binding revealed through PET imaging

Placzek MS, Schroeder FA, Che T, Wey HY, Neelamegam R, Wang C, Roth BL, Hooker JM. ACS Chem Neurosci. 2018. PMID: 30212182.

Docking for EP4R antagonists active against inflammatory pain

Gahbauer S, DeLeon C, Braz JM, Craik V, Kang HJ, Wan X, Huang XP, Billesbølle CB, Liu Y, Che T, Deshpande I, Jewell M, Fink EA, Kondratov IS, Moroz YS, Irwin JJ, Basbaum AI, Roth BL, Shoichet BK. Nat Commun. 2023 Dec. PMID: 38057319.

Fentanyl-related designers drugs W-18 and W-15 lack appreciable opioid activity in vitro and in vivo

Huang XP, Che T, Mangano TJ, Le Rouzic V, Pan YX, Majumdar S, Cameron MD, Baumann MH, Pasternak GW, Roth BL. J Clin Invest insight, 2017. PMID: 29202454.

GPCR-G protein selectivity revealed by structural pharmacology

Bernhard SM*, Han J*, Che T. FEBS J. 2023 Dec. PMID: 38151714.

Identification of the first marine-derived opioid receptor “balanced” agonist with a signaling profile that resembles the endorphins

Johnson TA, Milan-Lobo L, Che T, Ferwerda M, Lambu E, McIntosh NL, Li F, He L, Lorig-Roach N, Crews P, Whistler JL. ACS Chem Neurosci. 2016. PMID: 27744679.

In silico design of novel probes for the atypical opioid receptor MRGPRX2

Lansu K*, Karpiak J*, Liu J, Huang XP, McCorvy JD, Kroeze WK, Che T, Nagase H, Carroll FI, Jin J, Shoichet BK, Roth BL. Nat Chem Biol. 2017; 13(5):529-536. PMID: 28288109.

Kratom Alkaloids as Probes for Opioid Receptor Function: Pharmacological Characterization of Minor Indole and Oxindole Alkaloids from Kratom

Chakraborty S, Uprety R, Daibani AE, Rouzic VL, Hunkele A, Appourchaux K, Eans SO, Nuthikattu N, Jilakara R, Thammavong L, Pasternak GW, Pan YX, McLaughlin JP, Che T, Majumdar S. ACS Chem Neurosci. 2021. PMID: 34213886.

Measuring Drug-Induced Changes in Metabolite Populations of Live Bacteria: Real Time Analysis by Raman Spectroscopy

Carey PR, Whitmer GR, Yoon MJ, Lombardo MN, Pusztai-Carey M, Heidari-Torkabadi H, Che T. J Phys Chem B. 2018 Jun 21;122(24):6377-6385. PMID: 29792435.

Measuring propargyl-linked drug populations inside bacterial cells, and their interaction with a dihydrofolate reductase target, by Raman microscopy

Heidari-Torkabadi H, Che T, Lombardo MN, Wright DL, Anderson AC, Carey PR. Biochemistry. 2015; 54(17):2719-26. PMID: 25871808.

Molecular basis of opioid receptor signaling

Che T# and Roth BL#. Cell. 2023. Review. PMID: 37995655.

Nanobodies as sensors of GPCR activation and signaling

El Daibani A, Che T#. Methods Cell Biol. 2021. PMID: 34752331.

Nanobody-enabled monitoring of kappa opioid receptor states.

Che T#, English J, Krumm BE, Kim K, Pardon E, Olsen RHJ, Wang S, Zhang S, Diberto JF, Sciaky N, Carroll FI, Steyaert J, Wacker D, Roth BL#. Nat Commun. 2020. PMID: 32123179

Phosphoproteomics Illuminates Opioid Actions

Che T, Roth BL. Biochemistry. 2018. PMID: 30179451.

Raman spectra of interchanging beta-lactamase inhibitor intermediates on the millisecond time scale

Heidari Torkabadi H*, Che T*, Shou J, Shanmugam S, Crowder MW, Bonomo RA, Pusztai-Carey M, Carey PR. J Am Chem Soc. 2013; 135(8):2895-8. PMID: 3624989.

Spotlight on Nociceptin/Orphanin FQ Receptor in the Treatment of Pain

El Daibani A, Che T#. Molecules. 2022. PMID: 35163856.

Structural determinants of 5-HT2B receptor activation and biased agonism

McCorvy JD*, Wacker D*, Wang S*, Agegnehu B, Olsen RHJ, Che T, Jin J, Roth BL. Nat Struct Mol Biol. 2018 Aug 20. PMID: 30127358.

Structural Insights Accelerate the Discovery of Opioid Alternatives

Che T#, Roth BL#. Annual Review of Biochemistry. 2021. PMID: 33756098.

Structure determination of inactive-state GPCRs with a universal nanobody

Robertson MJ, Papasergi-Scott MM, He F, Seven AB, Meyerowitz JG, Panova O, Peroto MC, Che T, Skiniotis G. Nat Struct Mol Biol. 2022. PMID: 36396979.

Structure of a Hallucinogen-Activated Gq-Coupled 5-HT2A Serotonin Receptor

Kim K*, Che T*, Panova O*, DiBerto JF, Lyu JK, Krumm BE, Wacker D, Robertson MJ, Seven AB, Nichols DE, Shoichet BK, Skiniotis G, Roth BL. Cell. 2020. PMID: 32946782.

Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone

Wang S, Che T, Levit A, Shoichet BK, Wacker D, Roth BL. Nature. 2018 Mar 8;555(7695):269-273. PMID: 29466326.

Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor

Che T, Majumdar S, Zaidi SA, Ondachi P, McCorvy JD, Wang S, Mosier PD, Uprety R, Vardy E, Krumm BE, Han GW, Lee MY, Pardon E, Steyaert J, Huang XP, Strachan RT, Tribo AR, Pasternak GW, Carroll FI, Stevens RC, Cherezov V, Katritch V, Wacker D, Roth BL. Cell. 2018;172(1-2):55-67. PMID: 29307491.

Structure-based design of bitopic ligands for the micro-opioid receptor

Faouzi A*, Wang H*, Zaidi SA*, DiBerto JF*, Che T*, Qu Q, Robertson MJ, Madasu MK, El Daibani A, Varga BR, Zhang T, Ruiz C, Liu S, Xu J, Appourchaux K, Slocum ST, Eans SO, Cameron MD, AI-Hasani R, Pan YX, Roth BL, McLaughlin JP#, Skiniotis G#, Katritch V#, Kobilka BK#, Majumdar S#. Nature. 2023. PMID: 36450356.

The different inhibition mechanisms of OXA-1 and OXA-24 beta-lactamases are determined by the stability of active site carboxylated lysine

Che T, Bethel CR, Pusztai-Carey M, Bonomo RA, Carey PR. J Biol Chem. 2014; 289(9):6152-64. PMID: 3937681.