Publications

bioRxiv preprints

Mosure SA, Shang J, Brust R, Zheng J, Griffin PR, Kojetin DJ. (2018) Structural basis of altered potency and efficacy displayed by a major in vivo metabolite of the anti-diabetic PPARγ drug pioglitazone. [bioRxiv 351346] status: submitted

Shang J, Brust R, Mosure SA, Bass J, Munoz-Tello P, Lin H, Hughes TS, Tang M, Ge Q, Kamekenca TM, Kojetin DJ. (2018) Coincident binding of synthetic and natural ligands to the nuclear receptor PPARγ. [bioRxiv 252817] status: under revision

2018

Brust R, Shang J, Fuhrmann J, Bass J, Cano A, Heidari Z, Chrisman I, Blayo A-L, Griffin PR, Kamenecka TM, Kojetin DJ. (2018) A structural mechanism for directing inverse agonism of PPARγ. Nature Communications (accepted on 2018-10-15; in press) [bioRxiv 245852]

de Vera IMS, Munoz-Tello P, Dharmarajan V, Marciano DP, Matta-Camacho E, Giri PK, Shang J, Hughes TS, Rance M, Griffin PR, Kojetin DJ. (2018) Defining a canonical ligand-binding pocket in the orphan nuclear receptor Nurr1. Structure (accepted on 2018-10-05; in press) [bioRxiv 278440]

Zheng J, Corzo C, Chang MR, Shang J, Lam VQ, Brust R, Blayo A-L, Bruning JB, Kamekencka TM, Kojetin DJ, Griffin PR. (2018) Chemical crosslinking mass spectrometry reveals the conformational landscape of the activation helix of PPARγ; a model for ligand-dependent antagonism. Structure (accepted on 2018-05-23; in press) [pubmed] [journal]

Chrisman IM, Nemetchek MD, de Vera IMS, Shang J, Heidari Z, Long Y, Reys-Caballero H, Galindo-Murillo R, Cheatham III TE, Blayo A-L, Shin Y, Fuhrmann J, Griffin PR, Kamenecka TM, Kojetin DJ, Hughes TS. (2018) Defining a conformational ensemble that directs activation of PPARγ. Defining a conformational ensemble that directs activation of PPARγ. Nature Communications 9(1):1794 [pubmed] [journal]

Hudson WH, Vera IMS, Nwachukwu JC, Weikum ER, Herbst AG, Yang Q, Bain DL, Nettles KW, Kojetin DJ, Ortlund EA. (2018) Cryptic glucocorticoid receptor-binding sites pervade genomic NF-κB response elements. Nature Communications 9(1):1337 [pubmed]

2017

de Vera IMS, Zheng J, Novick S, Shang J, Hughes TS, Brust R, Munoz-Tello P, Gardner Jr WJ, Marciano DP, Kong X, Griffin PR, and Kojetin DJ. (2017) Synergistic Regulation of Coregulator/Nuclear Receptor Interaction by Ligand and DNA. Structure 2017 25(10):1506-1518 [pubmed]

Weikum ER, de Vera IMS, Nwachukwu JC, Hudson WH, Nettles KW, Kojetin DJ, and Ortlund EA. (2017) Tethering Not Required: the Glucocorticoid Receptor Binds Directly to Activator Protein-1 Recognition Motifs to Repress Inflammatory Genes. Nucleic Acids Research 45(14):8596-8608 [pubmed]

Nwachukwu JC, Srinivasan S, Bruno NE, Nowak J, Wright NJ, Minutolo F, Rangarajan ES, Izard T, Yao XQ, Grant BJ, Kojetin DJ, Elemento O, Katzenellenbogen JA, and Nettles KW. (2017) Systems Structural Biology Analysis of Ligand Effects on ERalpha Predicts Cellular Response to Environmental Estrogens and Anti-hormone Therapies. Cell Chemical Biology 24(1):35-45

Brust R, Lin H, Fuhrmann J, Asteian A, Kamenecka TM, and Kojetin DJ. (2017) Modification of the Orthosteric PPARgamma Covalent Antagonist Scaffold Yields an Improved Dual-Site Allosteric Inhibitor. ACS Chemical Biology 12(4):969-978

2016

Thenin-Houssier S, de Vera IM, Pedro-Rosa L, Brady A, Richard A, Konnick B, Opp S, Buffone C, Fuhrmann J, Kota S, Billack B, Pietka-Ottlik M, Tellinghuisen T, Choe H, Spicer T, Scampavia L, Diaz-Griffero F, Kojetin DJ, and Valente ST. (2016) Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication. Antimicrob Agents Chemother 60(4):2195-2208

Hughes TS, Shang J, Brust R, de Vera IMS, Fuhrmann J, Ruiz C, Cameron MD, Kamenecka TM, and Kojetin DJ. (2016) Probing the Complex Binding Modes of the PPARgamma Partial Agonist 2-Chloro-N-(3-chloro-4-((5-chlorobenzo[d]thiazol-2-yl)thio)phenyl)-4-(trifluorome thyl)benzenesulfonamide (T2384) to Orthosteric and Allosteric Sites with NMR Spectroscopy. Journal of Medicinal Chemistry 59(22):10335-10341

Hudson WH, Kossmann BR, de Vera IM, Chuo SW, Weikum ER, Eick GN, Thornton JW, Ivanov IN, Kojetin DJ, and Ortlund EA. (2016) Distal substitutions drive divergent DNA specificity among paralogous transcription factors through subdivision of conformational space. Proc Natl Acad Sci U S A 113(2):326-331

Hepowit NL, de Vera IM, Cao S, Fu X, Wu Y, Uthandi S, Chavarria NE, Englert M, Su D, Sll D, Kojetin DJ, and Maupin-Furlow JA. (2016) Mechanistic insight into protein modification and sulfur mobilization activities of noncanonical E1 and associated ubiquitin-like proteins of Archaea. FEBS J 283(19):3567-3586

Fuhrmann J, Subramanian V, Kojetin DJ, and Thompson PR. (2016) Activity-Based Profiling Reveals a Regulatory Link between Oxidative Stress and Protein Arginine Phosphorylation. Cell Chem Biol 23(8):967-977

de Vera IM, Giri PK, Munoz-Tello P, Brust R, Fuhrmann J, Matta-Camacho E, Shang J, Campbell S, Wilson HD, Granados J, Gardner WJ, Jr., Creamer TP, Solt LA, and Kojetin DJ. (2016) Identification of a Binding Site for Unsaturated Fatty Acids in the Orphan Nuclear Receptor Nurr1. ACS chemical biology 11(7):1795-1799

2015

Wang Y, Kojetin D, and Burris TP. (2015) Anti-proliferative actions of a synthetic REV-ERBalpha/beta agonist in breast cancer cells. Biochem Pharmacol 96(4):315-322

Marciano DP, Kuruvilla DS, Boregowda SV, Asteian A, Hughes TS, Garcia-Ordonez R, Corzo CA, Khan TM, Novick SJ, Park H, Kojetin DJ, Phinney DG, Bruning JB, Kamenecka TM, and Griffin PR. (2015) Pharmacological repression of PPARgamma promotes osteogenesis. Nature Communications 6(7443)

Kojetin DJ, Matta-Camacho E, Hughes TS, Srinivasan S, Nwachukwu JC, Cavett V, Nowak J, Chalmers MJ, Marciano DP, Kamenecka TM, Shulman AI, Rance M, Griffin PR, Bruning JB, and Nettles KW. (2015) Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. Nature communications 6(8013

Hughes TS, Wilson HD, de Vera IM, and Kojetin DJ. (2015) Deconvolution of Complex 1D NMR Spectra Using Objective Model Selection. PloS One 10(8):e0134474

2014

Nwachukwu JC, Srinivasan S, Bruno NE, Parent AA, Hughes TS, Pollock JA, Gjyshi O, Cavett V, Nowak J, Garcia-Ordonez RD, Houtman R, Griffin PR, Kojetin DJ, Katzenellenbogen JA, Conkright MD, and Nettles KW. (2014) Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network. eLife 3(e02057

Matta-Camacho E, Banerjee S, Hughes TS, Solt LA, Wang Y, Burris TP, and Kojetin DJ. (2014) Structure of REV-ERBbeta ligand-binding domain bound to a porphyrin antagonist. The Journal of Biological Chemistry 289(29):20054-20066

Kojetin DJ, and Burris TP. (2014) REV-ERB and ROR nuclear receptors as drug targets. Nature reviews. Drug discovery 13(3):197-216

Hughes TS, Giri PK, de Vera IM, Marciano DP, Kuruvilla DS, Shin Y, Blayo AL, Kamenecka TM, Burris TP, Griffin PR, and Kojetin DJ. (2014) An alternate binding site for PPARgamma ligands. Nature Communications 5(3571)

Hudson WH, Pickard MR, de Vera IM, Kuiper EG, Mourtada-Maarabouni M, Conn GL, Kojetin DJ, Williams GT, and Ortlund EA. (2014) Conserved sequence-specific lincRNA-steroid receptor interactions drive transcriptional repression and direct cell fate. Nature communications 5(5395)

2013

Srinivasan S, Nwachukwu JC, Parent AA, Cavett V, Nowak J, Hughes TS, Kojetin DJ, Katzenellenbogen JA, and Nettles KW. (2013) Ligand-binding dynamics rewire cellular signaling via estrogen receptor-alpha. Nature chemical biology 9(5):326-332

Kojetin DJ, and Burris TP. (2013) Small molecule modulation of nuclear receptor conformational dynamics: implications for function and drug discovery. Molecular pharmacology 83(1):1-8

Burris TP, Solt LA, Wang Y, Crumbley C, Banerjee S, Griffett K, Lundasen T, Hughes T, and Kojetin DJ. (2013) Nuclear receptors and their selective pharmacologic modulators. Pharmacological reviews 65(2):710-778

2012

Wang Y, Solt LA, Kojetin DJ, and Burris TP. (2012) Regulation of p53 stability and apoptosis by a ROR agonist. PloS one 7(4):e34921

Solt LA, Wang Y, Banerjee S, Hughes T, Kojetin DJ, Lundasen T, Shin Y, Liu J, Cameron MD, Noel R, Yoo SH, Takahashi JS, Butler AA, Kamenecka TM, and Burris TP. (2012) Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature 485(7396):62-68

Shin Y, Noel R, Banerjee S, Kojetin D, Song X, He Y, Lin L, Cameron MD, Burris TP, and Kamenecka TM. (2012) Small molecule tertiary amines as agonists of the nuclear hormone receptor Rev-erbalpha. Bioorganic & medicinal chemistry letters 22(13):4413-4417

Noel R, Song X, Shin Y, Banerjee S, Kojetin D, Lin L, Ruiz CH, Cameron MD, Burris TP, and Kamenecka TM. (2012) Synthesis and SAR of tetrahydroisoquinolines as Rev-erbalpha agonists. Bioorganic & medicinal chemistry letters 22(11):3739-3742

Hughes TS, Chalmers MJ, Novick S, Kuruvilla DS, Chang MR, Kamenecka TM, Rance M, Johnson BA, Burris TP, Griffin PR, and Kojetin DJ. (2012) Ligand and receptor dynamics contribute to the mechanism of graded PPARgamma agonism. Structure 20(1):139-150

Doerdelmann T, Kojetin DJ, Baird-Titus JM, Solt LA, Burris TP, and Rance M. (2012) Structural and biophysical insights into the ligand-free Pitx2 homeodomain and a ring dermoid of the cornea inducing homeodomain mutant. Biochemistry 51(2):665-676

Doerdelmann T, Kojetin DJ, Baird-Titus JM, and Rance M. (2012) (1)H, (1)(3)C and (1)(5)N chemical shift assignments for the human Pitx2 homeodomain in complex with a 22-base hairpin DNA. Biomolecular NMR assignments 6(1):79-81

2011

Zhang J, Chalmers MJ, Stayrook KR, Burris LL, Wang Y, Busby SA, Pascal BD, Garcia-Ordonez RD, Bruning JB, Istrate MA, Kojetin DJ, Dodge JA, Burris TP, and Griffin PR. (2011) DNA binding alters coactivator interaction surfaces of the intact VDR-RXR complex. Nature structural & molecular biology 18(5):556-563

Solt LA, Kojetin DJ, and Burris TP. (2011) The REV-ERBs and RORs: molecular links between circadian rhythms and lipid homeostasis. Future medicinal chemistry 3(5):623-638

Refaei MA, Combs A, Kojetin DJ, Cavanagh J, Caperelli C, Rance M, Sapitro J, and Tsang P. (2011) Observing selected domains in multi-domain proteins via sortase-mediated ligation and NMR spectroscopy. Journal of biomolecular NMR 49(1):3-7

Kumar N, Kojetin DJ, Solt LA, Kumar KG, Nuhant P, Duckett DR, Cameron MD, Butler AA, Roush WR, Griffin PR, and Burris TP. (2011) Identification of SR3335 (ML-176): a synthetic RORalpha selective inverse agonist. ACS chemical biology 6(3):218-222

Kojetin DJ, and Burris TP. (2011) A role for rev-erbalpha ligands in regulation of adipogenesis. Current pharmaceutical design 17(4):320-324

Kojetin D, Wang Y, Kamenecka TM, and Burris TP. (2011) Identification of SR8278, a synthetic antagonist of the nuclear heme receptor REV-ERB. ACS chemical biology 6(2):131-134

Doerdelmann T, Kojetin DJ, Baird-Titus JM, and Rance M. (2011) 1H, 13C and 15N chemical shift assignments for the human Pitx2 homeodomain and a R24H homeodomain mutant. Biomolecular NMR assignments 5(1):105-107

2001–2010

Crumbley C, Wang Y, Kojetin DJ, and Burris TP. (2010) Characterization of the core mammalian clock component, NPAS2, as a REV-ERBalpha/RORalpha target gene. The Journal of biological chemistry 285(46):35386-35392

Kojetin DJ, McLaughlin PD, Thompson RJ, Dubnau D, Prepiak P, Rance M, and Cavanagh J. (2009) Structural and motional contributions of the Bacillus subtilis ClpC N-domain to adaptor protein interactions. Journal of molecular biology 387(3):639-652

Sullivan DM, Bobay BG, Kojetin DJ, Thompson RJ, Rance M, Strauch MA, and Cavanagh J. (2008) Insights into the nature of DNA binding of AbrB-like transcription factors. Structure 16(11):1702-1713

Kojetin DJ, Burris TP, Jensen EV, and Khan SA. (2008) Implications of the binding of tamoxifen to the coactivator recognition site of the estrogen receptor. Endocrine-related cancer 15(4):851-870

Kojetin DJ, Sullivan DM, Thompson RJ, and Cavanagh J. (2007) Classification of response regulators based on their surface properties. Methods in enzymology 422(141-169

Kojetin DJ, McLaughlin PD, Thompson RJ, Venters RA, Rance M, and Cavanagh J. (2007) NMR assignment of the N-terminal repeat domain of Bacillus subtilis ClpC. Biomolecular NMR assignments 1(2):163-165

Kojetin DJ, Venters RA, Kordys DR, Thompson RJ, Kumar R, and Cavanagh J. (2006) Structure, binding interface and hydrophobic transitions of Ca2+-loaded calbindin-D(28K). Nature structural & molecular biology 13(7):641-647

Venters RA, Coggins BE, Kojetin D, Cavanagh J, and Zhou P. (2005) (4,2)D Projection--reconstruction experiments for protein backbone assignment: application to human carbonic anhydrase II and calbindin D(28K). Journal of the American Chemical Society 127(24):8785-8795

Ulrich DL, Kojetin D, Bassler BL, Cavanagh J, and Loria JP. (2005) Solution structure and dynamics of LuxU from Vibrio harveyi, a phosphotransferase protein involved in bacterial quorum sensing. Journal of molecular biology 347(2):297-307

Kojetin DJ, Thompson RJ, Benson LM, Naylor S, Waterman J, Davies KG, Opperman CH, Stephenson K, Hoch JA, and Cavanagh J. (2005) Structural analysis of divalent metals binding to the Bacillus subtilis response regulator Spo0F: the possibility for in vitro metalloregulation in the initiation of sporulation. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 18(5):449-466

Lutz W, Frank EM, Craig TA, Thompson R, Venters RA, Kojetin D, Cavanagh J, and Kumar R. (2003) Calbindin D28K interacts with Ran-binding protein M: identification of interacting domains by NMR spectroscopy. Biochemical and biophysical research communications 303(4):1186-1192

Kojetin DJ, Thompson RJ, and Cavanagh J. (2003) Sub-classification of response regulators using the surface characteristics of their receiver domains. FEBS letters 554(3):231-236

Helton TD, Kojetin DJ, Cavanagh J, and Horne WA. (2002) Alternative splicing of a beta4 subunit proline-rich motif regulates voltage-dependent gating and toxin block of Cav2.1 Ca2+ channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 22(21):9331-9339

Phillips CL, Arend LJ, Filson AJ, Kojetin DJ, Clendenon JL, Fang S, and Dunn KW. (2001) Three-dimensional imaging of embryonic mouse kidney by two-photon microscopy. The American journal of pathology 158(1):49-55