John H. Bushweller

Education

  • BA, Dartmouth College
  • PhD, University of California, Berkeley, CA
  • Postdoc, Eidgenössische Technische Hochschule, Zürich, Switzerland

Primary Appointment

  • Professor, Molecular Physiology and Biological Physics

Contact

Research Interest(s)

Drug Development Targeting Transcription Drivers in Cancer; Structure/Function Studies of Transcription Factor Drivers in Cancer; Structural Studies of Membrane Proteins

Research Description

Drug Development Targeting Transcription Drivers in Cancer Dysregulation of gene expression is a hallmark of all cancers. It is critical for self-renewal and chemo-resistance of cancer cells which contributes to the inability to completely eradicate cancer cells, thereby leading to relapse. The specific gene expression program that confers these properties derives from the aberrant activity of specific transcription factors which are drivers of disease. Clearly, the most direct and effective approach to alter this gene expression program is to directly target the activity of the transcription factors driving the disease. There are numerous examples of such transcription factor drivers in cancer such as fusion proteins of RUNX1 and CBFβ in leukemia, fusion proteins of ERG in prostate cancer and Ewing’s sarcoma, ETV-1 in melanoma, other members of the Ets family of transcription factors in a variety of different cancers, etc. Transcription factors have traditionally been viewed as “undruggable” due to the need to target more challenging protein-protein or protein nucleic acid interactions through which these proteins act. There are still relatively few examples of such agents for cancer treatment, with the MDM2-p53 inhibitors being one example of such an agent that has progressed to the clinic. We are exploring several unique approaches to target this important class of proteins for drug development. Illendula A, Pulikkan JA, Zong H, Grembecka J, Xue L, Sen S, Zhou Y, Boulton A, Kuntimaddi A, Gao Y, Rajewski RA, Guzman ML, Castilla LH, Bushweller JH. Chemical biology. A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice. Science. 2015 Feb 13;347(6223):779-84. PubMed PMID: 25678665; PubMed Central PMCID: PMC4423805.

Illendula A, Gilmour J, Grembecka J, Tirumala VSS, Boulton A, Kuntimaddi A, Schmidt C, , Wang L, John A. Pulikkan, Hongliang Zong, Mahmut Parlak, Cem Kuscu, Anna Pickin, Yunpeng Zhou, Yan Gao Y, Mishra L, Adli M, Castilla LH, Rajewski RA, Janes KA, Guzman ML, Bonifer C, and Bushweller JH. Small Molecule Inhibitor of CBFB-RUNX Binding for RUNX Transcription Factor Driven Cancers. EBioMedicine. 2016 8: 117-131. Pubmed PMID: 27428424; PubMed Central PMCID: PMC4919611.

Pulikkan JA, Hegde M, Belaghzal H, Illendula A, Yu J, Ahmed H, O’Hagan K, Ou J, Muller-Tidow C, Wolfe SA, Zhu LJ, Dekker J, Bushweller JH, Castilla LH. CBFβ-SMMHC inhibition leads to alteration of chromatin dynamics at MYC distal enhancers and abrogation of inv(16) leukemia. Cell. 2018 174(1):172-186.e21. Pubmed PMID: 29958106.

Structure/Function Studies of Transcription Factor Drivers in Cancer

Our lab is fundamentally interested in understanding, from a structural and biophysical perspective, the functioning of proteins involved in regulating transcription, particularly those involved in the dysregulation associated with the development of cancer. Structural and functional characterization of the native forms of these proteins and their relevant complexes via NMR spectroscopy, X-ray crystallography, and a variety of other techniques provides a baseline of understanding. Subsequent characterization of the oncoprotein forms then provides a detailed understanding of the molecular mechanism of oncogenesis associated with altered forms of these proteins. Such knowledge leads to novel avenues for the design of therapeutic agents to treat the cancers associated with these particular oncoproteins. A long-term focus has been structural studies of a novel transcription factor referred to as the core-binding factor (CBF). This heterodimeric protein is essential for hematopoietic development. Gene translocations associated with the genes coding for the two subunits of CBF produce novel fusion proteins which have been implicated as playing a role in more than 30% of acute leukemias. We have carried out extensive structural and functional studies of the oncoprotein forms of the two subunits of CBF that are associated with leukemia. We have extended these studies to the MLL protein, a key epigenetic regulator that is the target of chromosomal translocations in leukemia which are particularly poor prognosis. Cierpicki T, Risner LE, Grembecka J, Lukasik SM, Popovic R, Omonkowska M, Shultis DD, Zeleznik-Le NJ, Bushweller JH. Structure of the MLL CXXC domain-DNA complex and its functional role in MLL-AF9 leukemia. Nat Struct Mol Biol. 2010 Jan;17(1):62-8. PubMed PMID: 20010842; PubMed Central PMCID: PMC2908503.

Kuntimaddi A, Achille NJ, Thorpe J, Lokken AA, Singh R, Hemenway CS, Adli M, Zeleznik-Le NJ, Bushweller JH. Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 Di- and tri-methylation on target genes and transformation potential. Cell Rep. 2015 May 5;11(5):808-20. PubMed PMID: 25921540; PubMed Central PMCID: PMC4426023. Structural Studies of Membrane Proteins. A third focus for the lab is the application of solution NMR methods to the structure determination of membrane proteins. The vast majority of drug targets are membrane-embedded proteins. This class of proteins has presented significant challenges for structure determination by any method. We determined the structure of the 4 TM enzyme DsbB by solution NMR which established a paradigm for tackling this class of proteins by NMR. We recently completed the structure determination and mechanistic studies of the 6 TM membrane transporter CcdA.

Zhou Y, Cierpicki T, Jimenez RH, Lukasik SM, Ellena JF, Cafiso DS, Kadokura H, Beckwith J, Bushweller JH. NMR solution structure of the integral membrane enzyme DsbB: functional insights into DsbB-catalyzed disulfide bond formation. Mol Cell. 2008 Sep 26;31(6):896-908. PubMed PMID: 18922471; PubMed Central PMCID: PMC2622435.

Zhou Y and Bushweller JH. Solution Structure and Elevator Mechanism of the Membrane Electron Transporter CcdA. Nat Struct Mol Biol. 2018 25(2):163-169. Pubmed PMID: 29379172.

List of Publications in Pubmed

Selected Publications

  • Castilla L, Bushweller J. Molecular Basis and Targeted Inhibition of CBFβ-SMMHC Acute Myeloid Leukemia. Advances in experimental medicine and biology. 2017;962 229-244. PMID: 28299661
  • Choi A, Illendula A, Pulikkan J, Roderick J, Tesell J, Yu J, Hermance N, Zhu L, Castilla L, Bushweller J, Kelliher M. RUNX1 is required for oncogenic Myb and Myc enhancer activity in T cell acute lymphoblastic leukemia. Blood. 2017. PMID: 28790107
  • Margulieux K, Liebov B, Tirumala V, Singh A, Bushweller J, Nakamoto R, Hughes M. Bacillus anthracis Peptidoglycan Integrity Is Disrupted by the Chemokine CXCL10 through the FtsE/X Complex. Frontiers in microbiology. 2017;8 740. PMID: 28496437 | PMCID: PMC5406473
  • Tahirov T, Bushweller J. Structure and Biophysics of CBFβ/RUNX and Its Translocation Products. Advances in experimental medicine and biology. 2017;962 21-31. PMID: 28299648
  • Huang Y, Thoms J, Tursky M, Knezevic K, Beck D, Chandrakanthan V, Suryani S, Olivier J, Boulton A, Glaros E, Thomas S, Lock R, MacKenzie K, Bushweller J, Wong J, Pimanda J. MAPK/ERK2 phosphorylates ERG at serine 283 in leukemic cells and promotes stem cell signatures and cell proliferation. Leukemia. 2016;30(7): 1552-61. PMID: 27055868
  • Illendula A, Gilmour J, Grembecka J, Tirumala V, Boulton A, Kuntimaddi A, Schmidt C, Wang L, Pulikkan J, Zong H, Parlak M, Kuscu C, Pickin A, Zhou Y, Gao Y, Mishra L, Adli M, Castilla L, Rajewski R, Janes K, Guzman M, Bonifer C, Bushweller J. Small Molecule Inhibitor of CBFβ-RUNX Binding for RUNX Transcription Factor Driven Cancers. EBioMedicine. 2016;8 117-31. PMID: 27428424 | PMCID: PMC4919611
  • Illendula A, Pulikkan J, Zong H, Grembecka J, Xue L, Sen S, Zhou Y, Boulton A, Kuntimaddi A, Gao Y, Rajewski R, Guzman M, Castilla L, Bushweller J. Chemical biology. A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice. Science (New York, N.Y.). 2015;347(6223): 779-84. PMID: 25678665 | PMCID: PMC4423805
  • Kuntimaddi A, Achille N, Thorpe J, Lokken A, Singh R, Hemenway C, Adli M, Zeleznik-Le N, Bushweller J. Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 Di- and tri-methylation on target genes and transformation potential. Cell reports. 2015;11(5): 808-20. PMID: 25921540 | PMCID: PMC4426023
  • Xiao S, Brannon M, Zhao X, Fread K, Ellena J, Bushweller J, Finkielstein C, Armstrong G, Capelluto D. Tom1 Modulates Binding of Tollip to Phosphatidylinositol 3-Phosphate via a Coupled Folding and Binding Mechanism. Structure (London, England : 1993). 2015;23(10): 1910-20. PMID: 26320582
  • Lokken A, Achille N, Chang M, Lin J, Kuntimaddi A, Leach B, Malik B, Nesbit J, Zhang S, Bushweller J, Zeleznik-Le N, Hemenway C. Importance of a specific amino acid pairing for murine MLL leukemias driven by MLLT1/3 or AFF1/4. Leukemia research. 2014;38(11): 1309-15. PMID: 25282333 | PMCID: PMC4253547
  • Regan M, Horanyi P, Pryor E, Sarver J, Cafiso D, Bushweller J. Structural and dynamic studies of the transcription factor ERG reveal DNA binding is allosterically autoinhibited. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(33): 13374-9. PMID: 23898196 | PMCID: PMC3746864
  • Risner L, Kuntimaddi A, Lokken A, Achille N, Birch N, Schoenfelt K, Bushweller J, Zeleznik-Le N. Functional specificity of CpG DNA-binding CXXC domains in mixed lineage leukemia. The Journal of biological chemistry. 2013;288(41): 29901-10. PMID: 23990460 | PMCID: PMC3795288
  • Leach B, Kuntimaddi A, Schmidt C, Cierpicki T, Johnson S, Bushweller J. Leukemia fusion target AF9 is an intrinsically disordered transcriptional regulator that recruits multiple partners via coupled folding and binding. Structure (London, England : 1993). 2012;21(1): 176-83. PMID: 23260655 | PMCID: PMC3545106
  • Chen H, Ji F, Olman V, Mobley C, Liu Y, Zhou Y, Bushweller J, Prestegard J, Xu Y. Optimal mutation sites for PRE data collection and membrane protein structure prediction. Structure (London, England : 1993). 2011;19(4): 484-95. PMID: 21481772 | PMCID: PMC3099474
  • Corpora T, Roudaia L, Oo Z, Chen W, Manuylova E, Cai X, Chen M, Cierpicki T, Speck N, Bushweller J. Structure of the AML1-ETO NHR3-PKA(RIIα) complex and its contribution to AML1-ETO activity. Journal of molecular biology. 2010;402(3): 560-77. PMID: 20708017 | PMCID: PMC2945414
  • Früh V, Zhou Y, Chen D, Loch C, Ab E, Grinkova Y, Verheij H, Sligar S, Bushweller J, Siegal G. Application of fragment-based drug discovery to membrane proteins: identification of ligands of the integral membrane enzyme DsbB. Chemistry & biology. 2010;17(8): 881-91. PMID: 20797617 | PMCID: PMC4104428
  • Kamikubo Y, Zhao L, Wunderlich M, Corpora T, Hyde R, Paul T, Kundu M, Garrett L, Compton S, Huang G, Wolff L, Ito Y, Bushweller J, Mulloy J, Liu P. Accelerated leukemogenesis by truncated CBF beta-SMMHC defective in high-affinity binding with RUNX1. Cancer cell. 2010;17(5): 455-68. PMID: 20478528 | PMCID: PMC2874204
  • Park S, Osmers U, Raman G, Schwantes R, Diaz M, Bushweller J. The PHD3 domain of MLL acts as a CYP33-regulated switch between MLL-mediated activation and repression . Biochemistry. 2010;49(31): 6576-86. PMID: 20677832 | PMCID: PMC2916634
  • Cierpicki T, Bielnicki J, Zheng M, Gruszczyk J, Kasterka M, Petoukhov M, Zhang A, Fernandez E, Svergun D, Derewenda U, Bushweller J, Derewenda Z. The solution structure and dynamics of the DH-PH module of PDZRhoGEF in isolation and in complex with nucleotide-free RhoA. Protein science : a publication of the Protein Society. 2009;18(10): 2067-79. PMID: 19670212 | PMCID: PMC2786971
  • Cierpicki T, Risner L, Grembecka J, Lukasik S, Popovic R, Omonkowska M, Shultis D, Zeleznik-Le N, Bushweller J. Structure of the MLL CXXC domain-DNA complex and its functional role in MLL-AF9 leukemia. Nature structural & molecular biology. 2009;17(1): 62-8. PMID: 20010842 | PMCID: PMC2908503
  • Park S, Chen W, Cierpicki T, Tonelli M, Cai X, Speck N, Bushweller J. Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity. Blood. 2009;113(15): 3558-67. PMID: 19204326 | PMCID: PMC2668852
  • Park S, Speck N, Bushweller J. The role of CBFbeta in AML1-ETO's activity. Blood. 2009;114(13): 2849-50. PMID: 19779050
  • Roudaia L, Cheney M, Manuylova E, Chen W, Morrow M, Park S, Lee C, Kaur P, Williams O, Bushweller J, Speck N. CBFbeta is critical for AML1-ETO and TEL-AML1 activity. Blood. 2009;113(13): 3070-9. PMID: 19179469 | PMCID: PMC2662647
  • Zheng M, Cierpicki T, Momotani K, Artamonov M, Derewenda U, Bushweller J, Somlyo A, Derewenda Z. On the mechanism of autoinhibition of the RhoA-specific nucleotide exchange factor PDZRhoGEF. BMC structural biology. 2009;9 36. PMID: 19460155 | PMCID: PMC2695464
  • Erfurth F, Popovic R, Grembecka J, Cierpicki T, Theisler C, Xia Z, Stuart T, Diaz M, Bushweller J, Zeleznik-Le N. MLL protects CpG clusters from methylation within the Hoxa9 gene, maintaining transcript expression. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(21): 7517-22. PMID: 18483194 | PMCID: PMC2396713
  • Zhou Y, Cierpicki T, Jimenez R, Lukasik S, Ellena J, Cafiso D, Kadokura H, Beckwith J, Bushweller J. NMR solution structure of the integral membrane enzyme DsbB: functional insights into DsbB-catalyzed disulfide bond formation. Molecular cell. 2008;31(6): 896-908. PMID: 18922471 | PMCID: PMC2622435
  • Gorczynski M, Grembecka J, Zhou Y, Kong Y, Roudaia L, Douvas M, Newman M, Bielnicka I, Baber G, Corpora T, Shi J, Sridharan M, Lilien R, Donald B, Speck N, Brown M, Bushweller J. Allosteric inhibition of the protein-protein interaction between the leukemia-associated proteins Runx1 and CBFbeta. Chemistry & biology. 2007;14(10): 1186-97. PMID: 17961830
  • Liu Y, Chen W, Gaudet J, Cheney M, Roudaia L, Cierpicki T, Klet R, Hartman K, Laue T, Speck N, Bushweller J. Structural basis for recognition of SMRT/N-CoR by the MYND domain and its contribution to AML1/ETO's activity. Cancer cell. 2007;11(6): 483-97. PMID: 17560331 | PMCID: PMC1978186
  • Matheny C, Speck M, Cushing P, Zhou Y, Corpora T, Regan M, Newman M, Roudaia L, Speck C, Gu T, Griffey S, Bushweller J, Speck N. Disease mutations in RUNX1 and RUNX2 create nonfunctional, dominant-negative, or hypomorphic alleles. The EMBO journal. 2007;26(4): 1163-75. PMID: 17290219 | PMCID: PMC1852839
  • Cierpicki T, Kim M, Cooper D, Derewenda U, Bushweller J, Derewenda Z. The DC-module of doublecortin: dynamics, domain boundaries, and functional implications. Proteins. 2006;64(4): 874-82. PMID: 16835924
  • Cierpicki T, Liang B, Tamm L, Bushweller J. Increasing the accuracy of solution NMR structures of membrane proteins by application of residual dipolar couplings. High-resolution structure of outer membrane protein A. Journal of the American Chemical Society. 2006;128(21): 6947-51. PMID: 16719475 | PMCID: PMC2527590
  • Grembecka J, Cierpicki T, Devedjiev Y, Derewenda U, Kang B, Bushweller J, Derewenda Z. The binding of the PDZ tandem of syntenin to target proteins. Biochemistry. 2006;45(11): 3674-83. PMID: 16533050
  • Li Z, Lukasik S, Liu Y, Grembecka J, Bielnicka I, Bushweller J, Speck N. A mutation in the S-switch region of the Runt domain alters the dynamics of an allosteric network responsible for CBFbeta regulation. Journal of molecular biology. 2006;364(5): 1073-83. PMID: 17059830 | PMCID: PMC1783549
  • Liang B, Bushweller J, Tamm L. Site-directed parallel spin-labeling and paramagnetic relaxation enhancement in structure determination of membrane proteins by solution NMR spectroscopy. Journal of the American Chemical Society. 2006;128(13): 4389-97. PMID: 16569016 | PMCID: PMC3199951
  • Liu Y, Cheney M, Gaudet J, Chruszcz M, Lukasik S, Sugiyama D, Lary J, Cole J, Dauter Z, Minor W, Speck N, Bushweller J. The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO's activity. Cancer cell. 2006;9(4): 249-60. PMID: 16616331
  • Brautigan D, Brown M, Grindrod S, Chinigo G, Kruszewski A, Lukasik S, Bushweller J, Horal M, Keller S, Tamura S, Heimark D, Price J, Larner A, Larner J. Allosteric activation of protein phosphatase 2C by D-chiro-inositol-galactosamine, a putative mediator mimetic of insulin action. Biochemistry. 2005;44(33): 11067-73. PMID: 16101290
  • Cierpicki T, Bushweller J, Derewenda Z. Probing the supramodular architecture of a multidomain protein: the structure of syntenin in solution. Structure (London, England : 1993). 2005;13(2): 319-27. PMID: 15698575
  • Li Y, Han X, Lai A, Bushweller J, Cafiso D, Tamm L. Membrane structures of the hemifusion-inducing fusion peptide mutant G1S and the fusion-blocking mutant G1V of influenza virus hemagglutinin suggest a mechanism for pore opening in membrane fusion. Journal of virology. 2005;79(18): 12065-76. PMID: 16140782 | PMCID: PMC1212637
  • Lukasik S, Cierpicki T, Borloz M, Grembecka J, Everett A, Bushweller J. High resolution structure of the HDGF PWWP domain: a potential DNA binding domain. Protein science : a publication of the Protein Society. 2005;15(2): 314-23. PMID: 16384999 | PMCID: PMC2242466
  • Cierpicki T, Bushweller J. Charged gels as orienting media for measurement of residual dipolar couplings in soluble and integral membrane proteins. Journal of the American Chemical Society. 2004;126(49): 16259-66. PMID: 15584763
  • Gorczynski M, Leal R, Mooberry S, Bushweller J, Brown M. Synthesis and evaluation of substituted 4-aryloxy- and 4-arylsulfanyl-phenyl-2-aminothiazoles as inhibitors of human breast cancer cell proliferation. Bioorganic & medicinal chemistry. 2004;12(5): 1029-36. PMID: 14980616
  • Yan J, Liu Y, Lukasik S, Speck N, Bushweller J. CBFbeta allosterically regulates the Runx1 Runt domain via a dynamic conformational equilibrium. Nature structural & molecular biology. 2004;11(9): 901-6. PMID: 15322525
  • Cierpicki T, Kim M, Otlewski J, Derewenda Z, Bushweller J. Assignment of 1H, 13C and 15N resonances of the N-terminal microtubule-binding domain of human doublecortin. Journal of biomolecular NMR. 2003;25(1): 81-2. PMID: 12567003
  • Everett A, Bushweller J. Hepatoma derived growth factor is a nuclear targeted mitogen. Current drug targets. 2003;4(5): 367-71. PMID: 12816346
  • Kim M, Cierpicki T, Derewenda U, Krowarsch D, Feng Y, Devedjiev Y, Dauter Z, Walsh C, Otlewski J, Bushweller J, Derewenda Z. The DCX-domain tandems of doublecortin and doublecortin-like kinase. Nature structural biology. 2003;10(5): 324-33. PMID: 12692530
  • Li Z, Yan J, Matheny C, Corpora T, Bravo J, Warren A, Bushweller J, Speck N. Energetic contribution of residues in the Runx1 Runt domain to DNA binding. The Journal of biological chemistry. 2003;278(35): 33088-96. PMID: 12807882
  • Tamm L, Abildgaard F, Arora A, Blad H, Bushweller J. Structure, dynamics and function of the outer membrane protein A (OmpA) and influenza hemagglutinin fusion domain in detergent micelles by solution NMR. FEBS letters. 2003;555(1): 139-43. PMID: 14630334
  • Zhang L, Li Z, Yan J, Pradhan P, Corpora T, Cheney M, Bravo J, Warren A, Bushweller J, Speck N. Mutagenesis of the Runt domain defines two energetic hot spots for heterodimerization with the core binding factor beta subunit. The Journal of biological chemistry. 2003;278(35): 33097-104. PMID: 12807883
  • Zhang L, Lukasik S, Speck N, Bushweller J. Structural and functional characterization of Runx1, CBF beta, and CBF beta-SMMHC. Blood cells, molecules & diseases. 2003;30(2): 147-56. PMID: 12732176
  • Lukasik S, Zhang L, Corpora T, Tomanicek S, Li Y, Kundu M, Hartman K, Liu P, Laue T, Biltonen R, Speck N, Bushweller J. Altered affinity of CBF beta-SMMHC for Runx1 explains its role in leukemogenesis. Nature structural biology. 2002;9(9): 674-9. PMID: 12172539
  • Yan J, Corpora T, Pradhan P, Bushweller J. MQ-hCN-based pulse sequences for the measurement of 13C1'-1H1', 13C1'-15N, 1H1'-15N, 13C1'-13C2', 1H1'-13C2',13C6/8-1H6/8, 13C6/8-15N, 1H6/8-15N, 13C6-13C5, 1H6-13C5 dipolar couplings in 13C, 15N-labeled DNA (and RNA). Journal of biomolecular NMR. 2002;22(1): 9-20. PMID: 11885985
  • Arora A, Abildgaard F, Bushweller J, Tamm L. Structure of outer membrane protein A transmembrane domain by NMR spectroscopy. Nature structural biology. 2001;8(4): 334-8. PMID: 11276254
  • Han X, Bushweller J, Cafiso D, Tamm L. Membrane structure and fusion-triggering conformational change of the fusion domain from influenza hemagglutinin. Nature structural biology. 2001;8(8): 715-20. PMID: 11473264
  • Yan J, Bushweller J. An optimized PCR-based procedure for production of 13C/15N-labeled DNA. Biochemical and biophysical research communications. 2001;284(2): 295-300. PMID: 11394876
  • CBF--a biophysical perspective. Seminars in cell & developmental biology. 2000;11(5): 377-82. PMID: 11105902
  • Bailey-Kellogg C, Widge A, Kelley J, Berardi M, Bushweller J, Donald B. The NOESY jigsaw: automated protein secondary structure and main-chain assignment from sparse, unassigned NMR data. Journal of computational biology : a journal of computational molecular cell biology. 2000;7(3): 537-58. PMID: 11108478
  • Tang Y, Crute B, Kelley J, Huang X, Yan J, Shi J, Hartman K, Laue T, Speck N, Bushweller J. Biophysical characterization of interactions between the core binding factor alpha and beta subunits and DNA. FEBS letters. 2000;470(2): 167-72. PMID: 10734228
  • Tang Y, Shi J, Zhang L, Davis A, Bravo J, Warren A, Speck N, Bushweller J. Energetic and functional contribution of residues in the core binding factor beta (CBFbeta ) subunit to heterodimerization with CBFalpha. The Journal of biological chemistry. 2000;275(50): 39579-88. PMID: 10984496
  • Berardi M, Bushweller J. Binding specificity and mechanistic insight into glutaredoxin-catalyzed protein disulfide reduction. Journal of molecular biology. 1999;292(1): 151-61. PMID: 10493864
  • Berardi M, Sun C, Zehr M, Abildgaard F, Peng J, Speck N, Bushweller J. The Ig fold of the core binding factor alpha Runt domain is a member of a family of structurally and functionally related Ig-fold DNA-binding domains. Structure (London, England : 1993). 1999;7(10): 1247-56. PMID: 10545320
  • Huang X, Peng J, Speck N, Bushweller J. Solution structure of core binding factor beta and map of the CBF alpha binding site. Nature structural biology. 1999;6(7): 624-7. PMID: 10404216
  • Song W, Sullivan M, Legare R, Hutchings S, Tan X, Kufrin D, Ratajczak J, Resende I, Haworth C, Hock R, Loh M, Felix C, Roy D, Busque L, Kurnit D, Willman C, Gewirtz A, Speck N, Bushweller J, Li F, Gardiner K, Poncz M, Maris J, Gilliland D. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nature genetics. 1999;23(2): 166-75. PMID: 10508512
  • Berardi M, Pendred C, Bushweller J. Preparation, characterization, and complete heteronuclear NMR resonance assignments of the glutaredoxin (C14S)-ribonucleotide reductase B1 737-761 (C754S) mixed disulfide. Biochemistry. 1998;37(17): 5849-57. PMID: 9558318
  • Chen X, Mariappan S, Kelley J, Bushweller J, Bradbury E, Gupta G. A PCR-based method for uniform 13C/15N labeling of long DNA oligomers. FEBS letters. 1998;436(3): 372-6. PMID: 9801151
  • Huang X, Crute B, Sun C, Tang Y, Kelley J, Lewis A, Hartman K, Laue T, Speck N, Bushweller J. Overexpression, purification, and biophysical characterization of the heterodimerization domain of the core-binding factor beta subunit. The Journal of biological chemistry. 1998;273(4): 2480-7. PMID: 9442100
  • Huang X, Speck N, Bushweller J. Complete heteronuclear NMR resonance assignments and secondary structure of core binding factor beta (1-141). Journal of biomolecular NMR. 1998;12(3): 459-60. PMID: 9835054
  • Kelley J, Bushweller J. 1H, 13C and 15N NMR resonance assignments of vaccinia glutaredoxin-1 in the fully reduced form. Journal of biomolecular NMR. 1998;12(2): 353-5. PMID: 9752005
  • Sun C, Berardi M, Bushweller J. The NMR solution structure of human glutaredoxin in the fully reduced form. Journal of molecular biology. 1998;280(4): 687-701. PMID: 9677297
  • Kelley J, Caputo T, Eaton S, Laue T, Bushweller J. Comparison of backbone dynamics of reduced and oxidized Escherichia coli glutaredoxin-1 using 15N NMR relaxation measurements. Biochemistry. 1997;36(16): 5029-44. PMID: 9125525
  • Sun C, Holmgren A, Bushweller J. Complete 1H, 13C, and 15N NMR resonance assignments and secondary structure of human glutaredoxin in the fully reduced form. Protein science : a publication of the Protein Society. 1997;6(2): 383-90. PMID: 9041640 | PMCID: PMC2143634
  • Crute B, Lewis A, Wu Z, Bushweller J, Speck N. Biochemical and biophysical properties of the core-binding factor alpha2 (AML1) DNA-binding domain. The Journal of biological chemistry. 1996;271(42): 26251-60. PMID: 8824275
  • Gribble G, Switzer F, Bushweller J, Jewett J, Brown J, Dion J, Bushweller C, Byrn M, Strouse C. Stereodynamics of 9,11-Diphenyl-10-azatetracyclo[6.3.0.0.(4,11)0.(5,9)]undecanes. Highly Restricted Nitrogen Inversion and Isolated Phenyl Rotation. X-ray Crystallographic, Dynamic NMR, and Molecular Mechanics Studies. The Journal of organic chemistry. 1996;61(13): 4319-4327. PMID: 11667332
  • Wang Q, Stacy T, Miller J, Lewis A, Gu T, Huang X, Bushweller J, Bories J, Alt F, Ryan G, Liu P, Wynshaw-Boris A, Binder M, Marín-Padilla M, Sharpe A, Speck N. The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo. Cell. 1996;87(4): 697-708. PMID: 8929538
  • Bushweller J, Billeter M, Holmgren A, Wüthrich K. The nuclear magnetic resonance solution structure of the mixed disulfide between Escherichia coli glutaredoxin(C14S) and glutathione. Journal of molecular biology. 1994;235(5): 1585-97. PMID: 8107093
  • Bushweller J, Holmgren A, Wüthrich K. Biosynthetic 15N and 13C isotope labelling of glutathione in the mixed disulfide with Escherichia coli glutaredoxin documented by sequence-specific NMR assignments. European journal of biochemistry. 1993;218(2): 327-34. PMID: 8269921
  • Szyperski T, Wider G, Bushweller J, Wüthrich K. 3D 13C-15N-heteronuclear two-spin coherence spectroscopy for polypeptide backbone assignments in 13C-15N-double-labeled proteins. Journal of biomolecular NMR. 1993;3(1): 127-32. PMID: 8448432
  • Bushweller J, Aslund F, Wüthrich K, Holmgren A. Structural and functional characterization of the mutant Escherichia coli glutaredoxin (C14----S) and its mixed disulfide with glutathione. Biochemistry. 1992;31(38): 9288-93. PMID: 1390715
  • Xia T, Bushweller J, Sodano P, Billeter M, Björnberg O, Holmgren A, Wüthrich K. NMR structure of oxidized Escherichia coli glutaredoxin: comparison with reduced E. coli glutaredoxin and functionally related proteins. Protein science : a publication of the Protein Society. 1992;1(3): 310-21. PMID: 1304339 | PMCID: PMC2142208
  • Bushweller J, Bartlett P. Investigation of an octapeptide inhibitor of Escherichia coli ribonucleotide reductase by transferred nuclear Overhauser effect spectroscopy. Biochemistry. 1991;30(33): 8144-51. PMID: 1868090
  • Sodano P, Xia T, Bushweller J, Björnberg O, Holmgren A, Billeter M, Wüthrich K. Sequence-specific 1H n.m.r. assignments and determination of the three-dimensional structure of reduced Escherichia coli glutaredoxin. Journal of molecular biology. 1991;221(4): 1311-24. PMID: 1942053