Publications | Nicholas G. Brown Lab

Most recent publications list
52. Bodrug T, Welsh KA, Bolhuis DL, Paulakonis E, Martinez-Chacin RC, Liu B, Pinkin N, Bonacci T, Cui L, Xu P, Roscow O, Amann SJ, Grishkovskaya I, Emanuele MJ, Harrison JS, Steimel JP, Hahn KM, Zhang W, Zhong ED, Haselbach D*, BrownNG*. *Corresponding Author. Time-resolved cryo-EM (TR-EM) analysis of substrate polyubiquitination by the RING E3 anaphase-promoting complex/cyclosome (APC/C). Nature Structural & Molecular Biology. 2023.

51. Hodáková Z*, Grishkovskaya I, Brunner HL, Bolhuis DL, Belačić K, Schleiffer A, Kotisch H, Brown NG*, Haselbach D*.*Corresponding Author. Cryo-EM structure of the chain-elongating E3 ligase UBR5. EMBO J. 2023 Jul 6;:e113348. doi: 10.15252/embj.2022113348. [Epub ahead of print] PubMed PMID: 37409633.

50. Botta S, de Prisco N, Chemiakine A, Brandt V, Cabaj M, Patel P, Doron-Mandel E, Treadway CJ, Jovanovic M, Brown NG, Soni RK, Gennarino VA. Dosage sensitivity to Pumilio1 variants in the mouse brain reflects distinct molecular mechanisms. EMBO J. 2023 Jun 1;42(11):e112721. doi: 10.15252/embj.2022112721. Epub 2023 Apr 18. PMID: 37070548.

49. Iskandar SE, Pelton JM, Wick ET, Bolhuis DL, Baldwin AS, Emanuele MJ, Brown NG, Bowers AA. Enabling Genetic Code Expansion and Peptide Macrocyclization in mRNA Display via a Promiscuous Orthogonal Aminoacyl-tRNA Synthetase. J Am Chem Soc. 2023 Jan 25;145(3):1512-1517. doi: 10.1021/jacs.2c11294. Epub 2023 Jan 11. PMID: 36630539.

48. Chen J, Bolhuis DL, Laggner C, Kong D, Yu L, Wang X, Emanuele MJ, Brown NG*, Liu P*. *Corresponding Author AtomNet-Aided OTUD7B Inhibitor Discovery and Validation. Cancers. 2023 Jan 14;15(2). doi: 10.3390/cancers15020517. PubMed PMID: 36672466; PubMed Central PMCID: PMC9856706.

47. Amann SJ, Keihsler D, Bodrug T, Brown NG, Haselbach D. Frozen in time: analyzing molecular dynamics with time- resolved cryo-EM. Structure. 2023 Jan 5;31(1):4-19. doi: 10.1016/j.str.2022.11.014. Epub 2022 Dec 29. PubMed PMID: 36584678; PubMed Central PMCID: PMC9825670.

46. Wick ET, Treadway CJ, Li Z, Nicely NI, Ren Z, Baldwin AS, Xiong Y, Harrison JS*, Brown NG*. *Corresponding Author. Insight into Viral Hijacking of CRL4 Ubiquitin Ligase through Structural Analysis of the pUL145-DDB1 Complex. J Virol. 2022 Aug 8;:e0082622. doi: 10.1128/jvi.00826-22.

45. Bolhuis DL, Martinez-Chacin RC, Welsh KA, Bodrug T, Cui L, Emanuele MJ, Brown NG*. *Corresponding Author. Examining the mechanistic relationship of APC/C^CDH1 and its interphase inhibitor EMI1. Protein Sci. 2022 Jun;31(6):e4324. doi: 10.1002/pro.4324.

44. Kandolf S, Grishkovskaya I, Belačić K, Bolhuis DL, Amann S, Foster B, Imre R, Mechtler K, Schleiffer A, Tagare HD, Zhong ED, Meinhart A, Brown NG, Haselbach D. Cryo-EM structure of the plant 26S proteasome. Plant Commun. 2022 May 9;3(3):100310. doi: 10.1016/j.xplc.2022.100310.

43. Umano A, Fang K, Qu Z, Scaglione JB, Altinok S, Treadway CJ, Wick ET, Paulakonis E, Karunanayake C, Chou S, Bardakjian TM, Gonzalez-Alegre P, Page RC, Schisler JC, Brown NG, Yan D, Scaglione KM. The molecular basis of spinocerebellar ataxia type 48 caused by a de novo mutation in the ubiquitin ligase CHIP. J Biol Chem. 2022 May;298(5):101899. doi: 10.1016/j.jbc.2022.101899.

42. Welsh KA, Bolhuis DL, Nederstigt AE, Boyer J, Temple BRS, Bonacci T, Gu L, Ordureau A, Harper JW, Steimel JP, Zhang Q, Emanuele MJ, Harrison JS*, Brown NG*. *Corresponding Author. Functional conservation and divergence of the helix-turn-helix motif of E2 ubiquitin-conjugating enzymes. EMBO J. 2022 Feb 1;41(3):e108823. doi: 10.15252/embj.2021108823.

41. Ferguson CJ, Urso O, Bodrug T, Gassaway BM, Watson ER, Prabu JR, Lara-Gonzalez P, Martinez-Chacin RC, Wu DY, Brigatti KW, Puffenberger EG, Taylor CM, Haas-Givler B, Jinks RN, Strauss KA, Desai A, Gabel HW, Gygi SP, Schulman BA, Brown NG, Bonni A. APC7 mediates ubiquitin signaling in constitutive heterochromatin in the developing mammalian brain. Mol Cell. 2022 Jan 6;82(1):90-105.e13. doi: 10.1016/j.molcel.2021.11.031.

40. Enrico TP, Stallaert W, Wick ET, Ngoi P, Wang X, Rubin SM, Brown NG, Purvis JE, Emanuele MJ. Cyclin F drives proliferation through SCF-dependent degradation of the retinoblastoma-like tumor suppressor p130/RBL2. Elife. 2021 Dec 1;10. doi: 10.7554/eLife.70691.

39. Bodrug T, Welsh KA, Hinkle M, Emanuele MJ, Brown NG*. *Corresponding Author. Intricate Regulatory Mechanisms of the Anaphase-Promoting Complex/Cyclosome and Its Role in Chromatin Regulation. Front Cell Dev Biol. 2021;9:687515. doi: 10.3389/fcell.2021.687515. eCollection 2021. Review.

38. Franks JL, Martinez-Chacin RC, Wang X, Tiedemann RL, Bonacci T, Choudhury R, Bolhuis DL, Enrico TP, Mouery RD, Damrauer JS, Yan F, Harrison JS, Major MB, Hoadley KA, Suzuki A, Rothbart SB, Brown NG*, Emanuele MJ*. *Corresponding Author. In silico APC/C substrate discovery reveals cell cycle-dependent degradation of UHRF1 and other chromatin regulators. PLoS Biol. 2020 Dec 11;18(12):e3000975. doi: 10.1371/journal.pbio.3000975.

37. Skrajna A, Goldfarb D, Kedziora KM, Cousins EM, Grant GD, Spangler CJ, Barbour EH, Yan X, Hathaway NA, Brown NG, Cook JG, Major MB, McGinty RK. Comprehensive nucleosome interactome screen establishes fundamental principles of nucleosome binding. Nucleic Acids Res. 2020 Sep 25;48(17):9415-9432. doi: 10.1093/nar/gkaa544.

36. Chen LL, Smith MD, Lv L, Nakagawa T, Li Z, Sun SC, Brown NG, Xiong Y, Xu YP. USP15 suppresses tumor immunity via deubiquitylation and inactivation of TET2. Sci Adv. 2020 Sep;6(38). doi: 10.1126/sciadv.abc9730.

35. Martinez-Chacin RC, Bodrug T, Bolhuis DL, Kedziora KM, Bonacci T, Ordureau A, Gibbs ME, Weissmann F, Qiao R, Grant GD, Cook JG, Peters JM, Wade Harper J, Emanuele MJ*, Brown NG*. *Corresponding Author. Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC/C for substrate priming. Nat Struct Mol Biol. 2020 Jun;27(6):550-560.

34. Sonn-Segev A, Belacic K, Bodrug T, Young G, VanderLinden RT, Schulman BA, Schimpf J, Friedrich T, Dip PV, Schwartz TU, Bauer B, Peters JM, Struwe WB, Benesch JLP, Brown NG*, Haselbach D*, Kukura P*. *Corresponding Author. Quantifying the heterogeneity of macromolecular machines by mass photometry. Nat Commun. 2020 Apr 14;11(1):1772. doi: 10.1038/s41467-020-15642-w.

33. Richeson KV, Bodrug T, Sackton KL, Yamaguchi M, Paulo JA, Gygi SP, Schulman BA, Brown NG, King RW. Paradoxical mitotic exit induced by a small molecule inhibitor of APC/CCdc20. Nat Chem Biol. 2020 May;16(5):546-555.

32. Bodrug T and Brown NG*. *Corresponding Author. UBE2S Learns Self-Control. Structure. 2019 Aug 6;27(8):1185-1187. Invited Commentary.

31. Watson ER, Grace CRR, Zhang W, Miller DJ, Davidson IF, Prabu JR, Yu S, Bolhuis DL, Kulko ET, Vollrath R, Haselbach D, Stark H, Peters JM, Brown NG, Sidhu SS, Schulman BA. Protein Engineering to Uncover Cryptic Ubiquitin-binding Sites: from a Ubiquitin-Variant Inhibitor of APC/C to K48 Chain Binding. PNAS. 2019 Aug 27;116(35):17280-17289.

30. Beggs GA, Zalucki YM, Brown NG, Rastegari S, Phillips RK, Palzkill T, Shafer W, Kumaraswami M, Brennan RG. Structural, biochemical and in vivo characterization of MtrR-mediated resistance to innate antimicrobials by the human pathogen Neisseria gonorrhoeae. J Bacteriol. 2019 Oct 15;201(20).

29. Watson ER, Brown NG, Peters JM, Stark H, Schulman BA. Posing the APC/C E3 Ubiquitin Ligase to Orchestrate Cell Division. Trends Cell Biol. 2019 Feb;29(2):117-134. Review.

28. Bonacci T, Suzuki A, Grant GD, Stanley N, Cook JG, Brown NG, Emanuele MJ. Cezanne/OTUD7B is a Cell Cycle-Regulated Deubiquitinase that Antagonizes the Degradation of APC/C Substrates. EMBO J. 2018 Aug 15;37(16). doi: 10.15252/embj.201798701.

Prior to 2017

27. Yamaguchi M, VanderLinden R, Weissmann F, Qiao R, Dube P, Brown NG, Haselbach D, Zhang W, Sidhu SS, Peters JM, Stark H, Schulman BA. Cryo-EM of Mitotic Checkpoint Complex-Bound APC/C Reveals Reciprocal and Conformational Regulation of Ubiquitin Ligation. Mol Cell. 2016 Aug 18;63(4):593-607.

26. Brown NG, VanderLinden R, Watson ER, Weissmann F, Ordureau A, Wu KP, Zhang W, Yu S, Mercredi PY, Harrison JS, Davidson IF, Qiao R, Lu Y, Dube P, Brunner MR, Grace CR, Miller DJ, Haselbach D, Jarvis MA, Yamaguchi M, Yanishevski D, Petzold G, Sidhu SS, Kuhlman B, Kirschner MW, Harper JW, Peters JM, Stark H, Schulman BA. Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C. Cell. 2016 Jun 2;165(6):1440-53.

25. Weissmann F, Petzold G, VanderLinden R, Huis In ‘t Veld PJ, Brown NG, Lampert F, Westermann S, Stark H, Schulman BA, Peters JM. biGBac enables rapid gene assembly for the expression of large multisubunit protein complexes. Proc Natl Acad Sci U S A. 2016 May 10;113(19):E2564-9.

24. Qiao R, Weissmann F, Yamaguchi M, Brown NG, VanderLinden R, Imre R, Jarvis MA, Brunner MR, Davidson IF, Litos G, Haselbach D, Mechtler K, Stark H, Schulman BA, Peters JM. Mechanism of APC/CCDC20 activation by mitotic phosphorylation. Proc Natl Acad Sci U S A. 2016 May 10;113(19):E2570-8.

23. Jarvis MA, Brown NG, Watson ER, VanderLinden R, Schulman BA, Peters JM. Measuring APC/C-Dependent Ubiquitylation In Vitro. Methods Mol Biol. 2016;1342:287-303.

22. Brown NG, VanderLinden R, Watson ER, Qiao R, Grace CR, Yamaguchi M, Weissmann F, Frye JJ, Dube P, Ei Cho S, Actis ML, Rodrigues P, Fujii N, Peters JM, Stark H, Schulman BA. RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex. Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5272-9.

21. Yamaguchi M, Yu S, Qiao R, Weissmann F, Miller DJ, VanderLinden R, Brown NG, Frye JJ, Peters JM, Schulman BA. Structure of an APC3-APC16 complex: insights into assembly of the anaphase-promoting complex/cyclosome. J Mol Biol. 2015 Apr 24;427(8):1748-64.

20. Adamski CJ, Cardenas AM, Brown NG, Horton LB, Sankaran B, Prasad BV, Gilbert HF, Palzkill T. Molecular basis for the catalytic specificity of the CTX-M extended-spectrum β-lactamases. Biochemistry. 2015 Jan 20;54(2):447-57.

19. Viskovska M, Anish R, Hu L, Chow DC, Hurwitz AM, Brown NG, Palzkill T, Estes MK, Prasad BV. Probing the sites of interactions of rotaviral proteins involved in replication. J Virol. 2014 Nov;88(21):12866-81.

18. Brown NG, Watson ER, Weissmann F, Jarvis MA, VanderLinden R, Grace CR, Frye JJ, Qiao R, Dube P, Petzold G, Cho SE, Alsharif O, Bao J, Davidson IF, Zheng JJ, Nourse A, Kurinov I, Peters JM, Stark H, Schulman BA. Mechanism of polyubiquitination by human anaphase-promoting complex: RING repurposing for ubiquitin chain assembly. Mol Cell. 2014 Oct 23;56(2):246-60.

17. Fryszczyn BG, Adamski CJ, Brown NG, Rice K, Huang W, Palzkill T. Role of β-lactamase residues in a common interface for binding the structurally unrelated inhibitory proteins BLIP and BLIP-II. Protein Sci. 2014 Sep;23(9):1235-46.

16. Frye JJ, Brown NG, Petzold G, Watson ER, Grace CR, Nourse A, Jarvis MA, Kriwacki RW, Peters JM, Stark H, Schulman BA. Electron microscopy structure of human APC/C(CDH1)-EMI1 reveals multimodal mechanism of E3 ligase shutdown. Nat Struct Mol Biol. 2013 Jul;20(7):827-35.

15. Brown NG, Chow DC, Palzkill T. BLIP-II is a highly potent inhibitor of Klebsiella pneumoniae carbapenemase (KPC-2). Antimicrob Agents Chemother. 2013 Jul;57(7):3398-401.

14. Brown NG, Chow DC, Ruprecht KE, Palzkill T. Identification of the β-lactamase inhibitor protein-II (BLIP-II) interface residues essential for binding affinity and specificity for class A β-lactamases. J Biol Chem. 2013 Jun 14;288(24):17156-66.

13. Deng Z, Huang W, Bakkalbasi E, Brown NG, Adamski CJ, Rice K, Muzny D, Gibbs RA, Palzkill T. Deep sequencing of systematic combinatorial libraries reveals β-lactamase sequence constraints at high resolution. J Mol Biol. 2012 Dec 7;424(3-4):150-67.

12. Uzunova K, Dye BT, Schutz H, Ladurner R, Petzold G, Toyoda Y, Jarvis MA, Brown NG, Poser I, Novatchkova M, Mechtler K, Hyman AA, Stark H, Schulman BA, Peters JM. APC15 mediates CDC20 autoubiquitylation by APC/C(MCC) and disassembly of the mitotic checkpoint complex. Nat Struct Mol Biol. 2012 Nov;19(11):1116-23.

11. Horton LB, Shanker S, Mikulski R, Brown NG, Phillips KJ, Lykissa E, Venkataram Prasad BV, Palzkill T. Mutagenesis of zinc ligand residue Cys221 reveals plasticity in the IMP-1 metallo-β-lactamase active site. Antimicrob Agents Chemother. 2012 Nov;56(11):5667-77.

10. Cai G, Deng L, Fryszczyn BG, Brown NG, Liu Z, Jiang H, Palzkill T, Song Y. Thermodynamic Investigation of Inhibitor Binding to 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase. ACS Med Chem Lett. 2012 Jun 14;3(6):496-500.

9. Brown NG, Horton LB, Huang W, Vongpunsawad S, Palzkill T. Analysis of the functional contributions of Asn233 in metallo-β-lactamase IMP-1. Antimicrob Agents Chemother. 2011 Dec;55(12):5696-702.

8. Shelburne SA 3rd, Olsen RJ, Makthal N, Brown NG, Sahasrabhojane P, Watkins EM, Palzkill T, Musser JM, Kumaraswami M. An amino-terminal signal peptide of Vfr protein negatively influences RopB-dependent SpeB expression and attenuates virulence in Streptococcus pyogenes. Mol Microbiol. 2011 Dec;82(6):1481-95.

7. Fryszczyn BG, Brown NG, Huang W, Balderas MA, Palzkill T. Use of periplasmic target protein capture for phage display engineering of tight-binding protein-protein interactions. Protein Eng Des Sel. 2011 Nov;24(11):819-28.

6. Brown NG, Chow DC, Sankaran B, Zwart P, Prasad BV, Palzkill T. Analysis of the binding forces driving the tight interactions between beta-lactamase inhibitory protein-II (BLIP-II) and class A beta-lactamases. J Biol Chem. 2011 Sep 16;286(37):32723-35.

5. Kim JJ, Casteel DE, Huang G, Kwon TH, Ren RK, Zwart P, Headd JJ, Brown NG, Chow DC, Palzkill T, Kim C. Co-crystal structures of PKG Iβ (92-227) with cGMP and cAMP reveal the molecular details of cyclic-nucleotide binding. PLoS One. 2011 Apr 19;6(4):e18413.

4. Brown NG, Pennington JM, Huang W, Ayvaz T, Palzkill T. Multiple global suppressors of protein stability defects facilitate the evolution of extended-spectrum TEM β-lactamases. J Mol Biol. 2010 Dec 17;404(5):832-46.

3. Brown NG, Palzkill T. Identification and characterization of beta-lactamase inhibitor protein-II (BLIP-II) interactions with beta-lactamases using phage display. Protein Eng Des Sel. 2010 Jun;23(6):469-78.

2. Brown NG, Shanker S, Prasad BV, Palzkill T. Structural and biochemical evidence that a TEM-1 beta-lactamase N170G active site mutant acts via substrate-assisted catalysis. J Biol Chem. 2009 Nov 27;284(48):33703-12.

1. Marciano DC, Brown NG, Palzkill T. Analysis of the plasticity of location of the Arg244 positive charge within the active site of the TEM-1 beta-lactamase. Protein Sci. 2009 Oct;18(10):2080-9.