Frank G. Whitby

Frank G. Whitby, PhD

Languages spoken: English, French

Academic Information

Departments Primary - Biochemistry

Education History

Undergraduate University of Denver
 BS
Doctoral Training Rice University
 PhD
Postdoctoral Fellowship University of California
 Postdoctoral Fellow
Postdoctoral Fellowship University of Utah
 Postdoctoral Fellow

Selected Publications

Journal Article

  1. Sung SS, Brassington AM, Grannatt K, Rutherford A, Whitby FG, Krakowiak PA, Jorde LB, Carey JC, Bamshad M (2003). Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes. Am J Hum Genet, 72(3), 681-90.
  2. Brassington AM, Sung SS, Toydemir RM, Le T, Roeder AD, Rutherford AE, Whitby FG, Jorde LB, Bamshad MJ (2003). Expressivity of Holt-Oram syndrome is not predicted by TBX5 genotype. Am J Hum Genet, 73(1), 74-85.
  3. Toydemir RM, Brassington AE, Bayrak-Toydemir P, Krakowiak PA, Jorde LB, Whitby FG, Longo N, Viskochil DH, Carey JC, Bamshad MJ (2006). A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome. Am J Hum Genet, 79(5), 935-41.
  4. Liu J, Durrant D, Yang HS, He Y, Whitby FG, Myszka DG, Lee RM (2005). The interaction between tBid and cardiolipin or monolysocardiolipin. Biochem Biophys Res Commun, 330(3), 865-70.
  5. Huete-Perez JA, Wu JC, Whitby FG, Wang CC (1995). Identification of the IMP binding site in the IMP dehydrogenase from Tritrichomonas foetus. Biochemistry, 34(42), 13889-94.
  6. Whitby FG, Luecke H, Kuhn P, Somoza JR, Huete-Perez JA, Phillips JD, Hill CP, Fletterick RJ, Wang CC (1997). Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase and the enzyme-product complex. Biochemistry, 36(35), 10666-74.
  7. Phillips JD, Parker TL, Schubert HL, Whitby FG, Hill CP, Kushner JP (2001). Functional consequences of naturally occurring mutations in human uroporphyrinogen decarboxylase. Blood, 98(12), 3179-85.
  8. Avila-Sakar AJ, Schmid MF, Li LS, Whitby FG, Phillips GN Jr, Chiu W (1993). Preliminary electron crystallographic analysis of ice-embedded tropomyosin crystals. J Struct Biol, 110(1), 67-74.
  9. Warby CA, Phillips JD, Bergonia HA, Whitby FG, Hill CP, Kushner JP (2009). Structural and kinetic characterization of mutant human uroporphyrinogen decarboxylases. Cell Mol Biol (Noisy-le-grand), 55(2), 40-5.
  10. Phillips JD, Whitby FG, Kushner JP, Hill CP (1997). Characterization and crystallization of human uroporphyrinogen decarboxylase. Protein Sci, 6(6), 1343-6.
  11. Johnston SC, Whitby FG, Realini C, Rechsteiner M, Hill CP (1997). The proteasome 11S regulator subunit REG alpha (PA28 alpha) is a heptamer. Protein Sci, 6(11), 2469-73.
  12. Clinton TR, Weinstock MT, Jacobsen MT, Szabo-Fresnais N, Pandya MJ, Whitby FG, Herbert AS, Prugar LI, McKinnon R, Hill CP, Welch BD, Dye JM, Eckert DM, Kay MS (2015). Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets. Protein Sci, 24(4), 446-63.
  13. Toydemir RM, Rutherford A, Whitby FG, Jorde LB, Carey JC, Bamshad MJ (2006). Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. Nat Genet, 38(5), 561-5.
  14. Pornillos O, Ganser-Pornillos BK, Kelly BN, Hua Y, Whitby FG, Stout CD, Sundquist WI, Hill CP, Yeager M (2009). X-ray structures of the hexameric building block of the HIV capsid. Cell, 137(7), 1282-92.
  15. Xiong Q, Ruan B, Whitby FG, Tuohy RP, Belanger TL, Kelley RI, Wilson WK, Schroepfer GJ (2002). A colorimetric assay for 7-dehydrocholesterol with potential application to screening for Smith-Lemli-Opitz syndrome. Chem Phys Lipids, 115(1-2), 1-15.
  16. Olson TM, Karst ML, Whitby FG, Driscoll DJ (2002). Myosin light chain mutation causes autosomal recessive cardiomyopathy with mid-cavitary hypertrophy and restrictive physiology. Circulation, 105(20), 2337-40.
  17. Whitby FG, Phillips JD, Kushner JP, Hill CP (1998). Crystal structure of human uroporphyrinogen decarboxylase. EMBO J, 17(9), 2463-71.
  18. Mathews MA, Schubert HL, Whitby FG, Alexander KJ, Schadick K, Bergonia HA, Phillips JD, Hill CP (2001). Crystal structure of human uroporphyrinogen III synthase. EMBO J, 20(21), 5832-9.
  19. Forster A, Whitby FG, Hill CP (2003). The pore of activated 20S proteasomes has an ordered 7-fold symmetric conformation. EMBO J, 22(17), 4356-64.
  20. Phillips JD, Whitby FG, Kushner JP, Hill CP (2003). Structural basis for tetrapyrrole coordination by uroporphyrinogen decarboxylase. EMBO J, 22(23), 6225-33.
  21. Scott A, Chung HY, Gonciarz-Swiatek M, Hill GC, Whitby FG, Gaspar J, Holton JM, Viswanathan R, Ghaffarian S, Hill CP, Sundquist WI (2005). Structural and mechanistic studies of VPS4 proteins. EMBO J, 24(20), 3658-69.
  22. Byington CL, Dunbrack RL Jr, Whitby FG, Cohen FE, Agabian N (1997). Entamoeba histolytica: computer-assisted modeling of phosphofructokinase for the prediction of broad-spectrum antiparasitic agents. Exp Parasitol, 87(3), 194-202.
  23. Luecke H, Prosise GL, Whitby FG (1997). Tritrichomonas foetus: a strategy for structure-based inhibitor design of a protozoan inosine-5'-monophosphate dehydrogenase. Exp Parasitol, 87(3), 203-11.
  24. Kang J, Gemberling M, Nakamura M, Whitby FG, Handa H, Fairbrother WG, Tantin D (2009). A general mechanism for transcription regulation by Oct1 and Oct4 in response to genotoxic and oxidative stress. Genes Dev, 23(2), 208-22.
  25. Whitby FG, Xia G, Pickart CM, Hill CP (1998). Crystal structure of the human ubiquitin-like protein NEDD8 and interactions with ubiquitin pathway enzymes. J Biol Chem, 273(52), 34983-91.
  26. Phillips JD, Whitby FG, Warby CA, Labbe P, Yang C, Pflugrath JW, Ferrara JD, Robinson H, Kushner JP, Hill CP (2004). Crystal structure of the oxygen-dependant coproporphyrinogen oxidase (Hem13p) of Saccharomyces cerevisiae. J Biol Chem, 279(37), 38960-8.
  27. Li YC, Chiang CW, Yeh HC, Hsu PY, Whitby FG, Wang LH, Chan NL (2008). Structures of prostacyclin synthase and its complexes with substrate analog and inhibitor reveal a ligand-specific heme conformation change. J Biol Chem, 283(5), 2917-26.
  28. Stadtmueller BM, Ferrell K, Whitby FG, Heroux A, Robinson H, Myszka DG, Hill CP (2010). Structural models for interactions between the 20S proteasome and its PAN/19S activators. J Biol Chem, 285(1), 13-7.
  29. Kemble DJ, Whitby FG, Robinson H, McCullough LL, Formosa T, Hill CP (2013). Structure of the Spt16 middle domain reveals functional features of the histone chaperone FACT. J Biol Chem, 288(15), 10188-94.
  30. Ruan B, Wilson WK, Pang J, Gerst N, Pinkerton FD, Tsai J, Kelley RI, Whitby FG, Milewicz DM, Garbern J, Schroepfer GJ Jr (2001). Sterols in blood of normal and Smith-Lemli-Opitz subjects. J Lipid Res, 42(5), 799-812.
  31. Whitby FG, Kent H, Stewart F, Stewart M, Xie X, Hatch V, Cohen C, Phillips GN Jr (1992). Structure of tropomyosin at 9 angstroms resolution. J Mol Biol, 227(2), 441-52.
  32. Whitby FG, Phillips JD, Hill CP, McCoubrey W, Maines MD (2002). Crystal structure of a biliverdin IXalpha reductase enzyme-cofactor complex. J Mol Biol, 319(5), 1199-210.
  33. Gonciarz MD, Whitby FG, Eckert DM, Kieffer C, Heroux A, Sundquist WI, Hill CP (2008). Biochemical and structural studies of yeast Vps4 oligomerization. J Mol Biol, 384(4), 878-95.
  34. Phillips JD, Warby CA, Whitby FG, Kushner JP, Hill CP (2009). Substrate shuttling between active sites of uroporphyrinogen decarboxylase is not required to generate coproporphyrinogen. J Mol Biol, 389(2), 306-14.
  35. Monroe N, Han H, Gonciarz MD, Eckert DM, Karren MA, Whitby FG, Sundquist WI, Hill CP (2014). The oligomeric state of the active Vps4 AAA ATPase. J Mol Biol, 426(3), 510-25.
  36. Olson TM, Doan TP, Kishimoto NY, Whitby FG, Ackerman MJ, Fananapazir L (2000). Inherited and de novo mutations in the cardiac actin gene cause hypertrophic cardiomyopathy. J Mol Cell Cardiol, 32(9), 1687-94.
  37. Olson TM, Kishimoto NY, Whitby FG, Michels VV (2001). Mutations that alter the surface charge of alpha-tropomyosin are associated with dilated cardiomyopathy. J Mol Cell Cardiol, 33(4), 723-32.
  38. Wada Y, McCright IJ, Whitby FG, Tsunoda I, Fujinami RS (1998). Replacement of loop II of VP1 of the DA strain with loop II of the GDVII strain of Theiler's murine encephalomyelitis virus alters neurovirulence, viral persistence, and demyelination. J Virol, 72(9), 7557-62.
  39. McCright IJ, Tsunoda I, Whitby FG, Fujinami RS (1999). Theiler's viruses with mutations in loop I of VP1 lead to altered tropism and pathogenesis. J Virol, 73(4), 2814-24.
  40. Tsunoda I, Wada Y, Libbey JE, Cannon TS, Whitby FG, Fujinami RS (2001). Prolonged gray matter disease without demyelination caused by Theiler's murine encephalomyelitis virus with a mutation in VP2 puff B. J Virol, 75(16), 7494-505.
  41. Welch BD, Francis JN, Redman JS, Paul S, Weinstock MT, Reeves JD, Lie YS, Whitby FG, Eckert DM, Hill CP, Root MJ, Kay MS (2010). Design of a potent D-peptide HIV-1 entry inhibitor with a strong barrier to resistance. J Virol, 84(21), 11235-44.
  42. Knowlton JR, Johnston SC, Whitby FG, Realini C, Zhang Z, Rechsteiner M, Hill CP (1997). Structure of the proteasome activator REGalpha (PA28alpha). Nature, 390(6660), 639-43.
  43. Lloyd SA, Whitby FG, Blair DF, Hill CP (1999). Structure of the C-terminal domain of FliG, a component of the rotor in the bacterial flagellar motor. Nature, 400(6743), 472-5.
  44. Whitby FG, Masters EI, Kramer L, Knowlton JR, Yao Y, Wang CC, Hill CP (2000). Structural basis for the activation of 20S proteasomes by 11S regulators. Nature, 408(6808), 115-20.
  45. Smith J, Bibikova M, Whitby FG, Reddy AR, Chandrasegaran S, Carroll D (2000). Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains. Nucleic Acids Res, 28(17), 3361-9.
  46. Whitby FG, Huete-Perez J, Luecke H, Wang CC (1995). Preliminary X-ray crystallographic analysis of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase. Proteins, 23(4), 598-603.
  47. Whitby FG, Phillips GN Jr (2000). Crystal structure of tropomyosin at 7 Angstroms resolution. Proteins, 38(1), 49-59.
  48. McCullough J, Fisher RD, Whitby FG, Sundquist WI, Hill CP (2008). ALIX-CHMP4 interactions in the human ESCRT pathway. Proc Natl Acad Sci U S A, 105(22), 7687-91.
  49. DeLa Cruz R, Whitby FG, Buczek O, Bulaj G (2003). Detergent-assisted oxidative folding of delta-conotoxins. J Pept Res, 61(4), 202-12.
  50. Forster A, Masters EI, Whitby FG, Robinson H, Hill CP (2005). The 1.9 A structure of a proteasome-11S activator complex and implications for proteasome-PAN/PA700 interactions. Mol Cell, 18(5), 589-99.
  51. Sadre-Bazzaz K, Whitby FG, Robinson H, Formosa T, Hill CP (2010). Structure of a Blm10 complex reveals common mechanisms for proteasome binding and gate opening. Mol Cell, 37(5), 728-35.
  52. VanderLinden RT, Hemmis CW, Schmitt B, Ndoja A, Whitby FG, Robinson H, Cohen RE, Yao T, Hill CP (2015). Structural basis for the activation and inhibition of the UCH37 deubiquitylase. Mol Cell, 57(5), 901-11.
  53. David J. Kemble, Laura L. McCullough, Frank G. Whitby, Tim Formosa, Christopher P. Hil (2015). FACT Disrupts Nucleosome Structure by Binding H2A-H2B with Conserved Peptide Motifshttp://dx.doi.org/10.1016/j.molcel.2015.09.008. Molecular cell, 60, 1-13.
  54. Zhang H, Constantine R, Vorobiev S, Chen Y, Seetharaman J, Huang YJ, Xiao R, Montelione GT, Gerstner CD, Davis MW, Inana G, Whitby FG, Jorgensen EM, Hill CP, Tong L, Baehr (2011). UNC119 is required for G protein trafficking in sensory neurons. Nature neuroscience, 14(7), 874-80.
  55. Bracken CD, Neighbor AM, Lamlenn KK, Thomas GC, Schubert HL, Whitby FG, Howard B (2011). Crystal structures of a halophilic archaeal malate synthase from Haloferax volcanii and comparisons with isoforms A and G. BMC structural biology, 11, 23.
  56. Alam SL, Langelier C, Whitby FG, Koirala S, Robinson H, Hill CP, Sundquist W (2006). Structural basis for ubiquitin recognition by the human ESCRT-II EAP45 GLUE domain. Nature structural & molecular biology, 13(11), 1029-30.
  57. Stowell MHB, Soltis SM, Kisker C, Peters JW, Schindelin H, Rees DC, Cascio D, Beamer L, Hart PJ, Wiener MC, Whitby F (1996). A Simple Device for Studying Macromolecular Crystals Under Moderate Gas Pressure (0.1 - 10 MPa). Journal of applied crystallography, 29, 608-13.
  58. Paine EL, Skalicky JJ, Whitby FG, Mackay DR, Ullman KS, Hill CP, Sundquist W (2023). The Calpain-7 protease functions together with the ESCRT-III protein IST1 within the midbody to regulate the timing and completion of abscission. eLife, 12,
  59. Espino-Sanchez TJ, Wienkers H, Marvin RG, Nalder SA, García-Guerrero AE, VanNatta PE, Jami-Alahmadi Y, Mixon Blackwell A, Whitby FG, Wohlschlegel JA, Kieber-Emmons MT, Hill CP, Sigala P (2023). Direct tests of cytochrome c and c(1) functions in the electron transport chain of malaria parasites. Proceedings of the National Academy of Sciences of the United States of America, 120(19), e2301047120.
  60. Ramiro IBL, Bjørn-Yoshimoto WE, Imperial JS, Gajewiak J, Salcedo PF, Watkins M, Taylor D, Resager W, Ueberheide B, Bräuner-Osborne H, Whitby FG, Hill CP, Martin LF, Patwardhan A, Concepcion GP, Olivera BM, Safavi-Hemami (2022). Somatostatin venom analogs evolved by fish-hunting cone snails: From prey capture behavior to identifying drug leads. Science advances, 8(12), eabk1410.
  61. Liu L, Tang M, Pragani R, Whitby FG, Zhang YQ, Balakrishnan B, Fang Y, Karavadhi S, Tao D, LeClair CA, Hall MD, Marugan JJ, Boxer M, Shen M, Hill CP, Lai K, Patnaik (2021). Structure-Based Optimization of Small Molecule Human Galactokinase Inhibitors. Journal of medicinal chemistry, 64(18), 13551-13571.
  62. Kessler JL, Kang G, Qin Z, Kang H, Whitby FG, Cheatham TE 3rd, Hill CP, Li Y, Yu S (2021). Peptoid Residues Make Diverse, Hyperstable Collagen Triple-Helices. Journal of the American Chemical Society, 143(29), 10910-10919.
  63. Smith AR, Weinstock MT, Siglin AE, Whitby FG, Francis JN, Hill CP, Eckert DM, Root MJ, Kay M (2019). Characterization of resistance to a potent D-peptide HIV entry inhibitor. Retrovirology, 16(1), 28.
  64. Hudson NO, Whitby FG, Buck-Koehntop B (2018). Structural insights into methylated DNA recognition by the C-terminal zinc fingers of the DNA reader protein ZBTB38. The Journal of biological chemistry, 293(51), 19835-19843.
  65. Sdano MA, Fulcher JM, Palani S, Chandrasekharan MB, Parnell TJ, Whitby FG, Formosa T, Hill C (2017). A novel SH2 recognition mechanism recruits Spt6 to the doubly phosphorylated RNA polymerase II linker at sites of transcription. eLife, 6,
  66. Currie SL, Lau DKW, Doane JJ, Whitby FG, Okon M, McIntosh LP, Graves B (2017). Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4 and ETV5. Nucleic acids research, 45(5), 2223-2241.
  67. McClelland LJ, Steele HB, Whitby FG, Mou TC, Holley D, Ross JB, Sprang SR, Bowler B (2016). Cytochrome c Can Form a Well-Defined Binding Pocket for Hydrocarbons. Journal of the American Chemical Society, 138(51), 16770-16778.
  68. Giesler RJ, Woodham PCS, Draper SRE, Spaltenstein P, Whitby FG, Hill CP, Kay M (2025). Protein chirality as a determinant of ligand affinity: insights from l- and d-streptavidin. Chemical science, 16(48), 23342-23350.
  69. Espino-Sanchez TJ, Wienkers H, Marvin RG, Nalder SA, García-Guerrero AE, VanNatta PE, Jami-Alahmadi Y, Blackwell AM, Whitby FG, Wohlschlegel JA, Kieber-Emmons MT, Hill CP, Sigala P (2023). Direct Tests of Cytochrome Function in the Electron Transport Chain of Malaria Parasites. bioRxiv,
  70. Wienkers HJ, Han H, Whitby FG, Hill C (2024). Vps4 substrate binding and coupled mechanisms of Vps4p substrate recruitment and release from autoinhibition. bioRxiv,
  71. Goodell DJ, Whitby FG, Mellem JE, Lei N, Brockie PJ, Maricq AJ, Eckert DM, Hill CP, Madsen DM, Maricq A (2024). Mechanistic and structural studies reveal NRAP-1-dependent coincident activation of NMDARs. Cell reports, 43(2), 113694.
  72. Smith MS, Billings WM, Whitby FG, Miller MB, Price J (2017). Enhancing a long-range salt bridge with intermediate aromatic and nonpolar amino acids. Organic & biomolecular chemistry, 15(28), 5882-5886.

Book Chapter

  1. Hill CP, Masters EI, Whitby FG (2002). The 11S regulators of 20S proteasome activity. In Zwickl P, Baumeister W (Eds.), Curr Top Microbiol Immunol (268, pp. 73-89). Germany: Springer-Verlag.

Book Review

  1. Suzanne G. Frayser, Thomas J. Whitb (1996). Studies in Human Sexuality: A Selected Guide. 195-6.

Case Report

  1. Rentz AC, Libbey JE, Fujinami RS, Whitby FG, Byington CL (2006). Investigation of treatment failure in neonatal echovirus 7 infection. Pediatr Infect Dis J, 25(3), 259-62.
  2. Phillips JD, Whitby FG, Stadtmueller BM, Edwards CQ, Hill CP, Kushner J (2007). Two novel uroporphyrinogen decarboxylase (URO-D) mutations causing hepatoerythropoietic porphyria (HEP). Translational research, 149(2), 85-91.

Other

  1. Whitby FG, Hill C (2007). A versatile platform for inactivation and destruction. Structure (London, England, 15(2), 137-8.
  2. Whitby F (1994). Structure of Tropomyosin at 7 Ångstroms Resolution. Thesis.