Medical College of Wisconsin
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Brian C. Smith PhD

Brian C. Smith PhD profile photo picture

Associate Professor

Institution: Medical College of Wisconsin
Department: Biochemistry

Member of the Cancer Center
Member of the Cardiovascular Center
Member of the Center for Disease Prevention Research (CDPR)

Research Experience

  • Alkylating Agents
  • Amino Acids, Peptides, and Proteins
  • Binding Sites
  • Biochemistry
  • Catalysis
  • Deuterium Exchange Measurement
  • Enzyme Activators
  • Enzyme Inhibitors
  • Enzymes and Coenzymes
  • Histone Code
  • Histone Deacetylases
  • Mass Spectrometry
  • Molecular Probes
  • Molecular Structure
  • Nitric Oxide Donors
  • Nitric Oxide Synthase
  • Peptide Library
  • Peptides
  • Protein Binding
  • Proteins
  • Proteomics
  • Reducing Agents
  • Sirtuins
  • Structure-Activity Relationship
  • Substrate Specificity
  • Methodologies and Techniques

  • Biochemistry
  • Biological Assay
  • Chromatography, Affinity
  • Electrophoresis
  • Mass Spectrometry
  • Models, Chemical
  • Models, Molecular
  • Mutagenesis
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Library
  • Protein Array Analysis
  • Proteomics
  • chemical synthesis
  • enzymology
  • MCW Program / Core Facilities

  • Redox Biology
  • Biochemistry
  • Publications (42)

  • Molecular mechanics and dynamic simulations of well-known Kabuki syndrome-associated KDM6A variants reveal putative mechanisms of dysfunction. (Chi YI, Stodola TJ, De Assuncao TM, Levrence EN, Tripathi S, Dsouza NR, Mathison AJ, Basel DG, Volkman BF, Smith BC, Lomberk G, Zimmermann MT, Urrutia R) Orphanet J Rare Dis 2021 Feb 05;16(1):66 PMID: 33546721 PMCID: PMC7866879 02/07/2021    
  • Cysteine sulfenylation by CD36 signaling promotes arterial thrombosis in dyslipidemia. (Yang M, Li W, Harberg C, Chen W, Yue H, Ferreira RB, Wynia-Smith SL, Carroll KS, Zielonka J, Flaumenhaft R, Silverstein RL, Smith BC) Blood Adv 2020 Sep 22;4(18):4494-4507 PMID: 32946569 PMCID: PMC7509873 SCOPUS ID: 2-s2.0-85092260584 09/19/2020    
  • Development of activity-based probes for the protein deacylase Sirt1. (Goetz CJ, Sprague DJ, Smith BC) Bioorg Chem 2020 11;104:104232 PMID: 32911193 PMCID: PMC7686039 09/11/2020    
  • ICEKAT: an interactive online tool for calculating initial rates from continuous enzyme kinetic traces. (Olp MD, Kalous KS, Smith BC) BMC Bioinformatics 2020 May 14;21(1):186 PMID: 32410570 PMCID: PMC7222511 05/16/2020       3 Citations
  • Human sirtuins are differentially sensitive to inhibition by nitrosating agents and other cysteine oxidants. (Kalous KS, Wynia-Smith SL, Summers SB, Smith BC) J Biol Chem 2020 06 19;295(25):8524-8536 PMID: 32371394 PMCID: PMC7307208 05/07/2020       2 Citations
  • Validation and Characterization of Five Distinct Novel Inhibitors of Human Cytomegalovirus. (Kapoor A, Ghosh AK, Forman M, Hu X, Ye W, Southall N, Marugan J, Keyes RF, Smith BC, Meyers DJ, Ferrer M, Arav-Boger R) J Med Chem 2020 04 23;63(8):3896-3907 PMID: 32191456 PMCID: PMC7386824 SCOPUS ID: 2-s2.0-85084027851 03/20/2020    
  • Covalent-Fragment Screening of BRD4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites. (Olp MD, Sprague DJ, Goetz CJ, Kathman SG, Wynia-Smith SL, Shishodia S, Summers SB, Xu Z, Statsyuk AV, Smith BC) ACS Chem Biol 2020 04 17;15(4):1036-1049 PMID: 32149490 PMCID: PMC7271629 03/10/2020       8 Citations
  • Non-sedating benzodiazepines cause paralysis and tissue damage in the parasitic blood fluke Schistosoma mansoni. (McCusker P, Mian MY, Li G, Olp MD, Tiruveedhula VVNPB, Rashid F, Golani LK, Verma RS, Smith BC, Cook JM, Chan JD) PLoS Negl Trop Dis 2019 11;13(11):e0007826 PMID: 31730614 PMCID: PMC6881066 11/16/2019    
  • Mitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses. (Chen Y, Yang M, Huang W, Chen W, Zhao Y, Schulte ML, Volberding P, Gerbec Z, Zimmermann MT, Zeighami A, Demos W, Zhang J, Knaack DA, Smith BC, Cui W, Malarkannan S, Sodhi K, Shapiro JI, Xie Z, Sahoo D, Silverstein RL) Circ Res 2019 12 06;125(12):1087-1102 PMID: 31625810 PMCID: PMC6921463 SCOPUS ID: 2-s2.0-85076330129 10/19/2019       13 Citations
  • Comparative and integrative metabolomics reveal that S-nitrosation inhibits physiologically relevant metabolic enzymes. (Bruegger JJ, Smith BC, Wynia-Smith SL, Marletta MA) J Biol Chem 2018 04 27;293(17):6282-6296 PMID: 29483187 PMCID: PMC5925818 02/28/2018       3 Citations
  • Calmodulin-induced Conformational Control and Allostery Underlying Neuronal Nitric Oxide Synthase Activation. (Hanson QM, Carley JR, Gilbreath TJ, Smith BC, Underbakke ES) J Mol Biol 2018 03 30;430(7):935-947 PMID: 29458127 02/20/2018       6 Citations
  • Nitric oxide antagonism to glioblastoma photodynamic therapy and mitigation thereof by BET bromodomain inhibitor JQ1. (Fahey JM, Stancill JS, Smith BC, Girotti AW) J Biol Chem 2018 04 06;293(14):5345-5359 PMID: 29440272 PMCID: PMC5892570 SCOPUS ID: 2-s2.0-85045064956 02/15/2018       16 Citations
  • Development and Validation of 2D Difference Intensity Analysis for Chemical Library Screening by Protein-Detected NMR Spectroscopy. (Egner JM, Jensen DR, Olp MD, Kennedy NW, Volkman BF, Peterson FC, Smith BC, Hill RB) Chembiochem 2018 03 02;19(5):448-458 PMID: 29239081 PMCID: PMC5844354 SCOPUS ID: 2-s2.0-85041064927 12/15/2017       1 Citation
  • Metabolically Derived Lysine Acylations and Neighboring Modifications Tune the Binding of the BET Bromodomains to Histone H4. (Olp MD, Zhu N, Smith BC) Biochemistry 2017 10 17;56(41):5485-5495 PMID: 28945351 PMCID: PMC5970795 09/26/2017       7 Citations
  • Mechanism of Sirt1 NAD+-dependent Protein Deacetylase Inhibition by Cysteine S-Nitrosation. (Kalous KS, Wynia-Smith SL, Olp MD, Smith BC) J Biol Chem 2016 Dec 02;291(49):25398-25410 PMID: 27756843 PMCID: PMC5207242 10/21/2016       20 Citations
  • Nitrosothiol formation and S-nitrosation signaling through nitric oxide synthases. (Wynia-Smith SL, Smith BC) Nitric Oxide 2017 Feb 28;63:52-60 PMID: 27720836 10/11/2016       19 Citations
  • Chemoproteomic Strategy to Quantitatively Monitor Transnitrosation Uncovers Functionally Relevant S-Nitrosation Sites on Cathepsin D and HADH2. (Zhou Y, Wynia-Smith SL, Couvertier SM, Kalous KS, Marletta MA, Smith BC, Weerapana E) Cell Chem Biol 2016 06 23;23(6):727-37 PMID: 27291402 PMCID: PMC4920707 06/14/2016       26 Citations
  • Reply: To PMID 25479138. (Shteyer E, Smith B) Gastroenterology 2015 Jul;149(1):261-2 PMID: 26025311 05/31/2015    
  • Nitric Oxide Mediates Biofilm Formation and Symbiosis in Silicibacter sp. Strain TrichCH4B. (Rao M, Smith BC, Marletta MA) mBio 2015 May 05;6(3):e00206-15 PMID: 25944856 PMCID: PMC4436077 05/07/2015       19 Citations
  • Truncating mutation in the nitric oxide synthase 1 gene is associated with infantile achalasia. (Shteyer E, Edvardson S, Wynia-Smith SL, Pierri CL, Zangen T, Hashavya S, Begin M, Yaacov B, Cinamon Y, Koplewitz BZ, Vromen A, Elpeleg O, Smith BC) Gastroenterology 2015 Mar;148(3):533-536.e4 PMID: 25479138 12/06/2014       27 Citations
  • Nitric oxide signaling (Surmeli NB, Underbakke ES, Smith BC, Wynia-Smith SL, Marletta MA) Comprehensive Inorganic Chemistry Vol. 3, 241-262 10/29/2014    
  • Molecular architecture of mammalian nitric oxide synthases. (Campbell MG, Smith BC, Potter CS, Carragher B, Marletta MA) Proc Natl Acad Sci U S A 2014 Sep 02;111(35):E3614-23 PMID: 25125509 PMCID: PMC4156747 08/16/2014       64 Citations
  • Nitric oxide synthase domain interfaces regulate electron transfer and calmodulin activation. (Smith BC, Underbakke ES, Kulp DW, Schief WR, Marletta MA) Proc Natl Acad Sci U S A 2013 Sep 17;110(38):E3577-86 PMID: 24003111 PMCID: PMC3780838 09/05/2013       64 Citations
  • Mechanisms of S-nitrosothiol formation and selectivity in nitric oxide signaling. (Smith BC, Marletta MA) Curr Opin Chem Biol 2012 Dec;16(5-6):498-506 PMID: 23127359 PMCID: PMC3518608 11/07/2012       137 Citations
  • Mechanism and kinetics of inducible nitric oxide synthase auto-S-nitrosation and inactivation. (Smith BC, Fernhoff NB, Marletta MA) Biochemistry 2012 Feb 07;51(5):1028-40 PMID: 22242685 PMCID: PMC3277664 01/17/2012       18 Citations
  • Structural and kinetic isotope effect studies of nicotinamidase (Pnc1) from Saccharomyces cerevisiae. (Smith BC, Anderson MA, Hoadley KA, Keck JL, Cleland WW, Denu JM) Biochemistry 2012 Jan 10;51(1):243-56 PMID: 22229411 PMCID: PMC3257521 01/11/2012       11 Citations
  • Hydrolysis of O-acetyl-ADP-ribose isomers by ADP-ribosylhydrolase 3. (Kasamatsu A, Nakao M, Smith BC, Comstock LR, Ono T, Kato J, Denu JM, Moss J) J Biol Chem 2011 Jun 17;286(24):21110-7 PMID: 21498885 PMCID: PMC3122172 04/19/2011       28 Citations
  • Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction. (Hallows WC, Yu W, Smith BC, Devries MK, Ellinger JJ, Someya S, Shortreed MR, Prolla T, Markley JL, Smith LM, Zhao S, Guan KL, Denu JM) Mol Cell 2011 Jan 21;41(2):139-49 PMID: 21255725 PMCID: PMC3101115 01/25/2011       251 Citations
  • SIRT3 substrate specificity determined by peptide arrays and machine learning. (Smith BC, Settles B, Hallows WC, Craven MW, Denu JM) ACS Chem Biol 2011 Feb 18;6(2):146-57 PMID: 20945913 PMCID: PMC3042044 10/16/2010       56 Citations
  • A continuous microplate assay for sirtuins and nicotinamide-producing enzymes. (Smith BC, Hallows WC, Denu JM) Anal Biochem 2009 Nov 01;394(1):101-9 PMID: 19615966 PMCID: PMC2752052 07/21/2009       91 Citations
  • Ure(k)a! Sirtuins Regulate Mitochondria. (Hallows WC, Smith BC, Lee S, Denu JM) Cell 2009 May 01;137(3):404-6 PMID: 19410538 PMCID: PMC3310393 05/05/2009       12 Citations
  • Mechanisms and molecular probes of sirtuins. (Smith BC, Hallows WC, Denu JM) Chem Biol 2008 Oct 20;15(10):1002-13 PMID: 18940661 PMCID: PMC2626554 10/23/2008       115 Citations
  • Chemical mechanisms of histone lysine and arginine modifications. (Smith BC, Denu JM) Biochim Biophys Acta 2009 Jan;1789(1):45-57 PMID: 18603028 PMCID: PMC2642981 07/08/2008       233 Citations
  • Mechanism-based inhibition of Sir2 deacetylases by thioacetyl-lysine peptide. (Smith BC, Denu JM) Biochemistry 2007 Dec 18;46(50):14478-86 PMID: 18027980 11/22/2007       101 Citations
  • Acetyl-lysine analog peptides as mechanistic probes of protein deacetylases. (Smith BC, Denu JM) J Biol Chem 2007 Dec 21;282(51):37256-65 PMID: 17951578 10/24/2007       96 Citations
  • Linking SIRT2 to Parkinson's disease. (Garske AL, Smith BC, Denu JM) ACS Chem Biol 2007 Aug 17;2(8):529-32 PMID: 17708669 08/22/2007       50 Citations
  • Sir2 deacetylases exhibit nucleophilic participation of acetyl-lysine in NAD+ cleavage. (Smith BC, Denu JM) J Am Chem Soc 2007 May 09;129(18):5802-3 PMID: 17439123 PMCID: PMC2568996 04/19/2007       62 Citations
  • Sirtuins caught in the act. (Smith BC, Denu JM) Structure 2006 Aug;14(8):1207-8 PMID: 16905094 08/15/2006       8 Citations
  • Sir2 protein deacetylases: evidence for chemical intermediates and functions of a conserved histidine. (Smith BC, Denu JM) Biochemistry 2006 Jan 10;45(1):272-82 PMID: 16388603 PMCID: PMC2519119 01/04/2006       79 Citations
  • Small molecule regulation of Sir2 protein deacetylases. (Grubisha O, Smith BC, Denu JM) FEBS J 2005 Sep;272(18):4607-16 PMID: 16156783 09/15/2005       117 Citations
  • Mechanism of human SIRT1 activation by resveratrol. (Borra MT, Smith BC, Denu JM) J Biol Chem 2005 Apr 29;280(17):17187-95 PMID: 15749705 03/08/2005       780 Citations
  • Coenzyme specificity of Sir2 protein deacetylases: implications for physiological regulation. (Schmidt MT, Smith BC, Jackson MD, Denu JM) J Biol Chem 2004 Sep 17;279(38):40122-9 PMID: 15269219 07/23/2004       118 Citations
  • Last update: 02/20/2021