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Stephen White, DPhil
Stephen White, DPhil

Stephen White, DPhil

Emeritus, St. Jude Faculty



BS – University of Bristol, United Kingdom (1974)
DPhil – University of Oxford, United Kingdom (1978)

Research interests

  • The discovery and optimization of small molecule inhibitors to block catalysis with emphasis on antibacterial and antiviral compounds
  • Bacterial lipid and phospholipid metabolism
  • The mechanisms by which enzymes accelerate chemical reactions during catalysis
  • Cancer drug discovery
  • Fundamental mechanisms of DNA repair pathways and their roles in cancer

Selected Publications

Tsytlonok M, Sanabria H, Wang Y, Felekyan S, Hemmen K, Phillips AH, Yun MK, Waddell MB, Park CG, Vaithiyalingam S, Iconaru L, White SW, Tompa P, Seidel CAM, Kriwacki R. Dynamic anticipation by Cdk2/Cyclin A-bound p27 mediates signal integration in cell cycle regulation. Nat Commun. 2019 10:1676.

Wang Q, Arnst KE, Wang Y, Kumar G, Ma D, White SW, Miller DD, Li W, Li W. Structure-Guided Design, Synthesis, and Biological Evaluation of (2-(1H-Indol-3-yl)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl) Methanone (ABI-231) Analogues Targeting the Colchicine Binding Site in Tubulin. J Med Chem. 62:6734-6750, 2019.

Arnst KE, Wang Y, Lei Z-N, Hwang D-J, Kumar G, Ma D, Parke DN, Chen Q, Yang J, White SW, Seagroves TN, Chen Z-S, Miller DD, Li W. Colchicine Binding Site Agent DJ95 Overcomes Drug Resistance and Exhibits Antitumor Efficacy. Mol. Pharmacol. 96:73-89, 2019.

Cuypers M, Subramanian C, Gullett JM, Frank MW, White SW, Rock CO. Acyl Chain Selectivity and Physiological Roles of Staphylococcus aureus Fatty Acid Binding Proteins. J Biol Chem 294:38-49, 2019.

Cuypers MG, Robertson RM, Knipling L, Waddell MB, Hinton DM, White SW. The Phage T4 MotA Transcription Factor Contains a Novel DNA Binding Motif that Specifically Recognizes Modified DNA.  NAR 46:5308-5318, 2018.

Sharma LK, Subramanian C, Yun M-K, Frank MW, White SW, Rock CO, Lee RE, Jackowski S. A Therapeutic Approach to Pantothenate Kinase Associated Neurodegeneration. Nature Comm., 9:1-15, 2018.

Griffith EC, Wallace MJ, Wu Y, Kumar G, Gajewski S, Jackson P, Phelps GA, Zheng Z, Rock CO, Lee RE, White SW. The Structural and Functional Basis for Recurring Sulfa Drug Resistance Mutations in Staphylococcus aureus Dihydropteroate Synthase. Front Microbio 9:1369, 2018.

 Jones JC, Kumar G, Barman S, Najera I, White SW, Webby RJ, Govorkova EA. Identification of the I38T PA substitution as a Resistance Marker to Next-generation Influenza Virus Endonuclease Inhibitors. MBio 9: e00430-18, 2018.

Yang J, Milasta S, Hu D,1, Al Tahan AM, Interiano RB, Zhou J, Davidson J, Low J, Lin W, Bao J, Goh P, Nathwani AC, Wang R, Wang Y, Ong SS, Boyd VA, Young B, Das S, Shelat A, Wu Y, Li Z, Zheng JJ, Mishra, A, Cheng Y, Qu C, Peng J, Green, DR, White, SW, Guy RK, Chen T, Davidoff, AM. Targeting Histone Demethylases with the Small Molecule Ciclopirox for Myc-driven Neuroblastoma. Cancer Res 77:4626-4638, 2017.

Robertson RM, Yao J, Gajewski S, Kumar, G, Martin EW, Rock CO, White SW. A Two-Helix Motif Positions the Active Site of Lysophosphatidic Acid Acyltransferase for Catalysis Within the Membrane Bilayer. Nat Struct Mol Biol, 24:666-671, 2017.

Beylkin D, Kumar G, Zhou W, Park J, Jeevan T, Lagisetti C, Harfoot R, Webby RJ, White SW, Webb TR. Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-2 Carboxamide Inhibitors of Influenza Virus Endonuclease. Sci Reports, 7:17139, 17419-6, 2017

Gajewski S, Waddell MB, Vaithiyalingam S, Nourse A, Li Z, Woetzel N, Alexander N, Meiler J, White SW. Structure and Mechanism of the Phage T4 Recombination Mediator Protein UvsY. PNAS 113:3275-3280, 2016.

Subramanian C, Yun MK, Yao J, Sharma LK, Lee RE, White SW, Jackowski S, Rock CO. Allosteric Regulation of Mammalian Pantothenate Kinase. J Biol Chem 291: 22302-22314, 2016.

Zhao Y, Shadrick WR, Wallace MJ, Wu Y, Griffith EC, Qi J, Yun MK, White SW, Lee RE. Pterin-sulfa conjugates as dihydropteroate synthase inhibitors and antibacterial agents. Bioorg Med Chem Lett 26:3950-3954, 2016.

Broussard TC, Miller DJ, Jackson P, Nourse A, White SW, Rock CO. Biochemical roles for conserved residues in the bacterial fatty acid binding protein family. J Biol Chem 291:6292-6303, 2016.

Song, M-S, Kumar G, Shadrick WR, Zhou W, Jeevan T, Li Z, Slavish PJ, Fabrizio TP, Yoon S-W, Webb TR, Webby RJ, White SW. Identification and characterization of influenza variants resistant to a viral endonuclease inhibitor. PNAS 113:3669-3674, 2016.

Hammoudeh DI, Daté M, Yun MK, Zhang W, Boyd VA, Follis AV, Griffith E, Lee RE, Bashford D, White SW. Identification and characterization of an allosteric inhibitory site on dihydropteroate synthase. ACS Chem Biol. 9:1294-1302, 2014.


Show More

He X, Byrd AK, Yun MK, Pemble CW 4th, Harrison D, Yeruva L, Dahl C, Kreuzer KN, Raney KD, White SW. The T4 phage SF1B helicase Dda is structurally optimized to perform DNA strand separation. Structure May 30, 2012.

Baughman BM, Slavish PJ, DuBois RM, Boyd VA, White SW, Webb TR. Identification of Influenza Endonuclease Inhibitors in a Targeted Fragment Library via a Novel Fluorescence Polarization Assay. ACS Chemical Biology 2012 (in press).

Yun M-K, Wu Y, Li Z, Zhao Y, Waddell MB, Ferreira AM, Lee RE, Bashford D, White SW. Catalysis and sulfa drug resistance in dihydropteroate synthase. Science 335:1110-14, 2012.

Gajewski S, Comeaux EQ, Jafari N, Bharatham N, Bashford D, White SW, van Waardenburg RCAM. Analysis of the active-site mechanism of Tyrosyl-DNA phosphodiesterase: A member of the phospholipase D superfamily. J Mol Biol 415:741-58, 2012.

Zhao Y, Hammoudeh D, Lin W, Das S, Yun MK, Li Z, Griffith E, Chen T, White SW, Lee RE. Development of a pterin-based fluorescent probe for screening dihydropteroate synthase. Bioconjug Chem 22:2110-7, 2011.

DuBois RM, Zaraket H, Reddivari M, Heath RJ, White SW, Russell CJ. Acid stability of the hemagglutinin protein regulates H5N1 influenza virus pathogenicity. PloS Pathog 7:e1002398, 2011.

Qi J, Virga KG, Das S, Zhao Y, Yun MK, White SW, Lee RE. Synthesis of bi-substrate state mimics of dihydropteroate synthase as potential inhibitors and molecular probes. Bioorg Med Chem 19:1298-1305, 2011.

Dubois RM, Aguilar-Yanez JM, Mendoza-Ochoa GI, Oropeza-Almazan Y, Schultz-Cherry S, Alvarez MM, White SW, Russell CJ. The receptor-binding domain of influenza virus hemagglutinin produced in Escherichia coli folds into its native, immunogenic structure. J Virol 85:855-872, 2011.

Gajewski S, Webb MR, Galkin V, Egelman EH, Kreuzer KN, White SW. Crystal structure of the phage T4 recombinase UvsX and its functional interaction with the T4 SF2 helicase UvsW. J Mol Biol405:65-76, 2011.

Pemble CW IV, Mehta PK, Mehra S, Li Z, Nourse A, Lee RE, White SW. Crystal structure of the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase•dihydropteroate synthase bifunctional enzyme from Francisella tularensis. PLoS One 5:e14165, 2010.

Leonardi R, Zhang YM, Yun MK, Zhou R, Zeng FY, Lin W, Cui J, Chen T, Rock CO, White SW, Jackowski S. Modulation of pantothenate kinase 3 activity by small molecules that interact with the substrate/allosteric regulatory domain. Chem Biol 17:892-902, 2010.

Aguilar-Yanez JM, Portillo-Lara R, Mendoza-Ochoa GI, Garcia-Echauri SA, Lopez-Pacheco F, Bulnex-Abundis D, Salgado-Gallegos J, Lara-Mayorga IM, Webb-Vargas Y, Leon-Angel FO, Rivero-Aranda RE, Oropeza-Almazan Y, Ruiz-Palacios GM, Zertuche-Guerra MI, Dubois RM, White SW, Schulz-Cherry S, Russell CJ, Alvarez MM. An influenza A/H1N1/2009 hemagglutinin vaccine produced in E. coli. PLos One 5:e11694, 2010.

Miller DJ, Zhang YM, Subramanian C, Rock CO, White SW. Structural basis for the transcription regulation of membrane lipid homeostasis. Nat Struct Mol Biol 17:971-975, 2010.

Hevener KE, Yun M-K, Qi J, Kerr ID, Babaoglu K, Hurdle JG, Balakrishnan K, White SW, Lee RE. Structural studies of pterin-based inhibitors of dihydropteroate synthase. J Med Chem 53:166-177, 2009.

Zhao W, Hevener KE, White SW, Lee RE, Boyett JM. A statistical framework to evaluate virtual screening. BMC Bioinformatics 10:225, 2009.

Hevener KE, Zhao W, Ball DM, Babaoglu K, Qi J, White SW, Lee RE. Validation of molecular docking programs for virtual screening against dihydropteroate synthase. J Chem Inf Model 49:444-460, 2009.

Jerga A, Miller DJ, White SW, Rock CO. Interfacial binding and conformational change in a soluble diacylglycerol kinase. J Biol Chem 284:7246-7254, 2009.

Miller DJ, Jerga A, Rock CO, White SW. Analysis of the Staphylococcus aureus DgkB structure reveals a common catalytic mechanism for the soluble diacylglycerol kinases. Structure 16:1036-1046, 2008.

Kerr ID, Sivakolundu S, Li Z, Buchsbaum JC, Knox LA, Kriwacki RW, White SW. Crystallographic and NMR analyses of UvsW and UvsW.1 from bacteriophage T4. J Biol Chem 282:34392-34400, 2007.

He X, van Waardenburg RC, Babaoglu K, Price AC, Nitiss KC, Nitiss JL, Bjornsti MA, White SW. Mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poison. J Mol Biol 372:1070-1081, 2007.

Yun M, Nourse A, White SW, Rock CO, Heath RJ. Crystal structure and allosteric regulation of the cytoplasmic Escherichia coli L-asparaginase 1. J Mol Biol 369:794-811, 2007.

Hong BS, Yun MK, Zhang Y-M, Chohnan S, Rock CO, White SW, Jackowski S, Park H-W, Leonardi R. Prokaryotic type II and type III pantothenate kinases: The same monomer fold creates dimers with distinct catalytic properties. Structure 14:1251-1261, 2006.

Zeitoun O, Santos NMD, Gardner LA, White SW, Bahouth SW. Mutagenesis within helix 6 of the human {beta}1-adrenergic receptor identifies lysine324 as a residue involved in imparting the high-affinity binding state of agonists. Molecular Pharmacology 70:838-850, 2006.

Nitiss KC, Malik M, He X, White SW, Nitiss JL. Tyrosyl DNA phosphodiesterase 1 (Tdp1) participates in the repair of Top2 mediated DNA damage. Proc Natl Acad Sci 103:8953-8958, 2006.

Santos NMD, Gardner LA, White SW, Bahouth SW. Characterization of the residues in helix 8 of the human beta 1-adrenergic receptor that are involved in coupling the receptor to G proteins. J Biol Chem 281:12896-12907, 2006.

Zhang Y-M, White SW, Rock CO. Inhibiting bacterial fatty acid synthesis. J Biol Chem 281:17541-17544, 2006.

Miller DJ, Zhang Y-M, Rock CO, White SW. Structure of RhIG, an essential beta-ketoacyl reductase in the rhamnolipid biosynthetic pathway of Pseudomonas aeruginosa. J Biol Chem 281:18025-18032, 2006.

Zhang Y-M, Hurlbert J, White SW, Rock CO. Roles of the active site water, histidine-303 and phenylalanine-396 in the catalytic mechanism of the elongation condensing enzyme of streptococcus pneumoniae. J Biol Chem 281:17390-17399, 2006.

Kim P, Zhang YM, Shenoy G, Nguyen QA, Boshoff HI, Manjunatha UH, Goodwin MB, Lonsdale J, Price AC, Miller DJ, Duncan K, White SW, Rock CO, Barry CE III, Dowd CS. Structure-activity relationships at the 5-position of thiolactomycin: an intact (5R)-isoprene unit is required for activity against the condensing enzymes from Mycobacterium tuberculosis and Escherichia coli. J Med Chem 49:159-171, 2006.

Last update: October 2019