Featured publications
We presented the first quantitative chemoproteomic method to identify CO₂-dependent lysine carboxylation (Lys-CO₂) in proteins. We used this method to explore the lysine carboxylome of the CO₂ responsive cyanobacterium Synechocystis sp. We identified 20 novel Lys-CO₂ sites including one within the metabolic sensor protein PII. Carboxylation of this lysine decreased PII binding to its regulatory effector ATP.
We developed a proteome-wide approach to monitor the thermostability effect of PTMs and used it to uncover the O-GlcNAc dependent meltome. Surprisingly, O-GlcNAc was predominantly destabilizing, a finding that challenged the predominant view of O-GlcNAc as being stabilizing. This method serves as a blueprint to study the thermostability effect of, in principle, any protein modification.
We leverage an emerging mass spectrometry fragmentation method called ultraviolet photodissociation to map the notoriously labile O-GlcNAc modification on proteins. We demonstrate the broad utility of this method and use it to discover new modification sites with unprecedented precision. We expect this method will be broadly useful for mapping labile PTMs on proteins and proteomes.
Complete publication list
2024
(32) Bhosale S., Kandalkar S., Gilormini P., Akintola O., Rowland R., Adabala P.J.P, King D.T., Deen M.C., Chen X., Davies G.J., Vocadlo D.J., Bennet A.J. Development of tunable mechanism-based carbasugar ligands that stabilize glycoside hydrolases through the formation of transient covalent intermediates. ACS Catal. 14(19): 14769-14779 (2024)
2023
2021
(27) Bouquet J., Auberger N., King D.T., Bordes A., Fontelle N., Nakagawa S., Madden Z., Proceviat C., Kato A., Desire J. Vocadlo D.J., Ashmus R.A., Blériot Y. Structural variation of the 3-acetamido-4,5,6-trihydroxyazepane iminosugar through epimerization and C-alkylation leads to low micromolar HexAB and NagZ inhibitors. Organ. & Biomol. Chem. DOI: 10.1039/D1OB02280F (2021)
(26) Ashmus R.A., Wang Y., González-Cuesta M., King D.T., Tiet B., Gilormini P., Fernandez J.M.G., Mellet C.O., Britton R., Vocadlo D.J. Rationale design of cell active C2-modified DGJ analogues for the inhibition of human beta-galactosidase A (GALA). Org. Biomol. Chem.19: 8057-8062 (2021)
(25) Mulligan V.K., Workman S., Sun T., Rettie S., Li X., Worrall L.J., Cravin T.W., King D.T., Hosseinzadeh P., Watkins A.M., Renfrew P.D., Guffy S., Labonte J.W., Moretti R., Bonneau R., Strynadka N.C.J., Baker D. Computationally designed peptide macrocycle inhibitors of New Delhi metallo-β-lactamase 1. Proc. Natl. Acad. Sci. U.S.A. 118: e2012800118 (2021)
2020
(24) McGuire B.E., Hettle A.G., Vickers C., King D.T., Vocadlo D.J., Boraston A.B. The structure of a family 110 glycoside hydrolase provides insight into the hydrolysis of β-(1,3)-galactosidic linkages in α-carrageenan and blood group antigens. J. Biol. Chem. 295(52): 18426-18435 (2020)
(23) King D.T.*, Escobar E.E.*, Serrano-Negrón J.E., Alteen M.G., Vocadlo D.J., Brodbelt J.S. Precision mapping of O-linked N-acetylglucosamine sites in proteins using ultraviolet photodissociation mass spectrometry. J. Am. Chem. Soc. 142: 11569-11577 (2020)
(22) Alexander J.A.N., Radaeva M., King D.T., Chambers H.F., Cherkasov A., Chatterjee S.S., Strynadka N.C.J. Structural analysis of avibactam mediated activation of the bla and mec divergons in methicillin-resistant Staphylococcus aureus. J. Biol. Chem. 295: 10870-10884 (2020)
2019 and earlier
(21) King D.T., Males A., Davies G.J., Vocadlo D.J. Molecular mechanisms regulating O-linked N-acetylglucosamine (O-GlcNAc)-processing enzymes. Curr. Opin. Chem. Biol. 53: 131-144 (2019)
(20) Sannikova N., Gerak C.A.N., Shidmoossavee F.S., King D.T., Samsi K.A.S., Lewis R.L., Bennet, A.J. Both chemical and non-chemical steps limit the catalytic efficiency of family 4 glycoside hydrolases. Biochemistry. 57: 3378-3386 (2018)
(19) King D.T.*, Sobhanifar, S.*, Strynadka N.C.J. Handbook of antimicrobial resistance: the mechanisms of resistance to β-lactam antibiotics. (eds. Gotte M., Berghuis A., Matlashewski G., Sheppard D., Wainberg M.A.) 177-201 (Springer, 2017)
(18) Alvarez-Dorta D., King D.T., Legigan T., Ide D., Adachi I., Deniaud D., Désiré J., Kato A., Vocadlo D.J., Gouin S.G., Blériot Y. Multivalency to inhibit and discriminate hexosaminidases. Chem. Eur. J. 23: 9022-9025 (2017)
(17) Bouquit J., King D.T., Vadlamani G., Lorga B., Kato A., Vocadlo D.J., Mark B., Blériot Y., Désiré J. Selective trihydroxylated azepane inhibitors of NagZ, a glycosidase involved in Pseudomonas aeruginosa resistance to β-lactam antibiotics. Org. Biomol. Chem. 15: 4609-4619 (2017)
(16) Roth C., Chan S., Offen W.A., Hemsworth G.R., Willems L., King D.T., Varghese V., Britton R., Vocadlo D.J., Davies G.J. Structural and functional insight into human O-GlcNAcase. Nat. Chem. Biol. 13: 610-612 (2017)
(15) King D.T., Sobhanifar S., Strynadka N.C.J. One ring to rule them all: current trends in combating bacterial resistance to the β-lactams. Prot. Sci. 25: 787-803 (2016)
(14) Sobhanifar S., Worrall L.J., King D.T., Wasney G.A., Baumann L., Gale R.T., Nosella M., Brown E.D., Withers S.G., Strynadka N.C.J. Structure and mechanism of Staphylococcus aureus TarS, the wall teichoic acid β-glycosyltransferase involved in methicillin resistance. PLoS Pathog. 12: e1006067 (2016)
(13) King D.T., Wasney G.A., Nosella M., Fong A., Strynadka N.C.J. Structural insights into inhibition of escherichia coli penicillin-binding protein 1b. J. Biol. Chem. 292: 979-993 (2016)
(12) King D.T.*, King A.M.*, French S., Brouillette E., Asli A., Alexander J.A.N., Vuckovic M., Parr T.R., Brown E.D., Malouin F., Strynadka N.C.J., Wright G.D. Structural and kinetic characterization of diazabicyclooctanes as dual inhibitors of both serine-β-lactamases and penicillin-binding proteins. ACS Chem. Biol. 11: 864-868 (2016)
(11) Ghavami A., Labbé G., Brem J., Goodfellow V.J., Marrone L., Tanner C.A., King D.T., Lam M., Strynadka N.C.J., Pillai D.R., Siemann S., Spencer J., Schofield C.J., and Dmitrienko G.I. Assays for drug discovery: synthesis and testing of novel nitrocefin analogues for use as β-lactamase substrates. Anal. Biochem. 486: 75-77 (2015)
(10) King D.T.*, King A.M.*, Lal S.M., Wright G.D., Strynadka N.C.J. Molecular mechanism of avibactam mediated β-lactamase inhibition. ACS Infect. Dis. 1: 175-184 (2015)
(9) Barnes M., van Rensburg G., Li W.M., Mehmood K., Mackedenski S., Chan C.M., King D.T., Miller A.L., Lee C.H. Molecular insights into the coding region determinant-binding protein-RNA interaction through site-directed mutagenesis in the heterogeneous nuclear ribonucleoprotein-K-homology domains. J. Biol. Chem. 290: 625-639 (2015)
(8) King A.M., Reid-Yu S.A., Wang W., King D.T., De Pascale G., Strynadka N.C., Walsh T.R., Coombes B.K., Wright G.D. Aspergillomarasmine A overcomes metallo-β-lactamase antibiotic resistance. Nature. 510: 503-506 (2014)
(7) King D.T., Lameignere E., Strynadka N.C. Structural insights into the lipoprotein outer membrane regulator of penicillin-binding-protein 1B. J. Biol. Chem. 289(27): 19245-19253 (2014)
(6) King D.T., Barnes M., Thomsen D., Lee C.H. Assessing specific oligonucleotides and small molecule antibiotics for the ability to inhibit the CRD-BP-CD44 RNA Interaction. PLoS One. 9: e91585 (2014)
(5) Sobhanifar S.*, King D.T.*, Strynadka N.C.J. Fortifying the wall: synthesis, regulation and degradation of bacterial peptidoglycan. Curr. Opin. Struct. Biol. 23: 695-703 (2013)
(4) King D.T., Strynadka N.C.J. Targeting metallo-β-lactamase enzymes in antibiotic resistance. Future Med. Chem. 5: 1243-1263 (2013)
(3) King D.T., Strynadka N.C.J. New delhi metallo-β-lactamase: insights into β-lactam recognition and inhibition. J. Am. Chem. Soc. 134: 11362-11365 (2012)
(2) King D.T., Strynadka N. Crystal structure of new delhi metallo-β-lactamase reveals molecular basis for antibiotic resistance. Protein Sci. 134: 1243-1263 (2011)
(1) Kim, W., King, D., Lee, C.H. RNA-cleaving properties of human apurinic/apyrimidinic endonuclease 1 (APE1). Int. J. Biochem. Mol. Biol. 1:12-25 (2010)