Faculty Appointments
Assistant Professor of Biochemistry
Education
Ph.D., Molecular Pharmacology and Physiology, Brown University, Providence, Rhode IslandB.S., Chemistry, Duke University, Durham, North Carolina
Office Address
639C Light Hall
2215 Garland Avenue
Nashville, TN 37204
2215 Garland Avenue
Nashville, TN 37204
Research Description
Macromolecular protein complex assembly is critical for maintaining human health. These precise interactions are necessary to modulate various cellular processes such as the activity of signaling pathways, feedback regulation, and the transport of molecules among partners. Unfortunately, there are numerous painful, debilitating, and life-threatening diseases that occur due to genetic mutations that prevent proper protein assembly. Our approach is to use X-ray crystallography and other complementary biochemical techniques to understand how these various mutations lead to changes in protein structure and function, thus preventing productive macromolecular assembly. We focus on areas of human health related to mitochondrial biology and metabolism. Specifically, we seek to understand the assembly mechanisms responsible for regulating heme biosynthesis, which is altered in several blood diseases.
Research Keywords
structural biology, biophysics, biochemistry, X-ray crystallography, mitochondria, protein structure-function, heme, hematology, metabolism, molecular biology
Publications
Chitrakar I, Roberson AB, Ayres-Galhardo PH, Brown BL. A reversible feedback mechanism regulating mitochondrial heme synthesis. J Biol Chem [print-electronic]. 2026 Feb; 302(2): 111089. PMID: 41443426, PMCID: PMC12856317, PII: S0021-9258(25)02941-2, DOI: 10.1016/j.jbc.2025.111089, ISSN: 1083-351X.
Taylor JL, Ayres-Galhardo PH, Brown BL. Elucidating the Role of Human ALAS2 C-terminal Mutations Resulting in Loss of Function and Disease. Biochemistry [print-electronic]. 2024 Jul 7/2/2024; 63(13): 1636-46. PMID: 38888931, PMCID: PMC11223264, DOI: 10.1021/acs.biochem.4c00066, ISSN: 1520-4995.
Brown BL. Heterologous Expression and Purification of Eukaryotic ALA Synthase from E. coli. Methods Mol Biol. 2024; 2839: 233-41. PMID: 39008257, DOI: 10.1007/978-1-0716-4043-2_13, ISSN: 1940-6029.
Tran JU, Brown BL. The yeast ALA synthase C-terminus positively controls enzyme structure and function. Protein Sci. 2023 Apr; 32(4): e4600. PMID: 36807942, PMCID: PMC10031213, DOI: 10.1002/pro.4600, ISSN: 1469-896X.
Taylor JL, Brown BL. Structural basis for dysregulation of aminolevulinic acid synthase in human disease. J Biol Chem [print-electronic]. 2022 Mar; 298(3): 101643. PMID: 35093382, PMCID: PMC8892079, PII: S0021-9258(22)00083-7, DOI: 10.1016/j.jbc.2022.101643, ISSN: 1083-351X.
Tran JU, Brown BL. Structural Basis for Allostery in PLP-dependent Enzymes. Front Mol Biosci. 2022; 9: 884281. PMID: 35547395, PMCID: PMC9081730, PII: 884281, DOI: 10.3389/fmolb.2022.884281, ISSN: 2296-889X.
Brown BL, Iverson TM. Handling heme with care. Nat Chem Biol. 2021 Jul; 17(7): 751-2. PMID: 34103722, PII: 10.1038/s41589-021-00821-7, DOI: 10.1038/s41589-021-00821-7, ISSN: 1552-4469.
Hung LY, Tanaka Y, Herbine K, Pastore C, Singh B, Ferguson A, Vora N, Douglas B, Zullo K, Behrens EM, Li Hui Tan T, Kohanski MA, Bryce P, Lin C, Kambayashi T, Reed DR, Brown BL, Cohen NA, Herbert DR. Cellular context of IL-33 expression dictates impact on anti-helminth immunity. Sci Immunol. 2020 Nov 11/13/2020; 5(53): PMID: 33188058, PII: 5/53/eabc6259, DOI: 10.1126/sciimmunol.abc6259, ISSN: 2470-9468.
Brown BL, Vieux EF, Kalastavadi T, Kim S, Chen JZ, Baker TA. N domain of the Lon AAA+ protease controls assembly and substrate choice. Protein Sci [print-electronic]. 2018 Nov 11/21/2018; PMID: 30461098, DOI: 10.1002/pro.3553, ISSN: 1469-896X.
Brown BL, Kardon JR, Sauer RT, Baker TA. Structure of the Mitochondrial Aminolevulinic Acid Synthase, a Key Heme Biosynthetic Enzyme. Structure [print-electronic]. 2018 Apr 4/3/2018; 26(4): 580-589.e4. PMID: 29551290, PMCID: PMC5894356, PII: S0969-2126(18)30052-2, DOI: 10.1016/j.str.2018.02.012, ISSN: 1878-4186.
Davis JR, Brown BL, Page R, Sello JK. Study of PcaV from Streptomyces coelicolor yields new insights into ligand-responsive MarR family transcription factors. Nucleic Acids Res [print-electronic]. 2013 Apr 4/1/2013; 41(6): 3888-900. PMID: 23396446, PMCID: PMC3616709, PII: gkt009, DOI: 10.1093/nar/gkt009, ISSN: 1362-4962.
Brown BL, Lord DM, Grigoriu S, Peti W, Page R. The Escherichia coli toxin MqsR destabilizes the transcriptional repression complex formed between the antitoxin MqsA and the mqsRA operon promoter. J. Biol. Chem [print-electronic]. 2013 Jan 1/11/2013; 288(2): 1286-94. PMID: 23172222, PMCID: PMC3543012, PII: M112.421008, DOI: 10.1074/jbc.M112.421008, ISSN: 1083-351X.
Wang X, Kim Y, Hong SH, Ma Q, Brown BL, Pu M, Tarone AM, Benedik MJ, Peti W, Page R, Wood TK. Antitoxin MqsA helps mediate the bacterial general stress response. Nat. Chem. Biol [print-electronic]. 2011 Jun; 7(6): 359-66. PMID: 21516113, PMCID: PMC3097263, PII: nchembio.560, DOI: 10.1038/nchembio.560, ISSN: 1552-4469.
Brown BL, Wood TK, Peti W, Page R. Structure of the Escherichia coli antitoxin MqsA (YgiT/b3021) bound to its gene promoter reveals extensive domain rearrangements and the specificity of transcriptional regulation. J. Biol. Chem [print-electronic]. 2011 Jan 1/21/2011; 286(3): 2285-96. PMID: 21068382, PMCID: PMC3023523, PII: M110.172643, DOI: 10.1074/jbc.M110.172643, ISSN: 1083-351X.
Brown BL, Page R. Preliminary crystallographic analysis of the Escherichia coli antitoxin MqsA (YgiT/b3021) in complex with mqsRA promoter DNA. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun [print-electronic]. 2010 Sep 9/1/2010; 66(Pt 9): 1060-3. PMID: 20823526, PMCID: PMC2935227, PII: S1744309110028617, DOI: 10.1107/S1744309110028617, ISSN: 1744-3091.
Brown BL, Grigoriu S, Kim Y, Arruda JM, Davenport A, Wood TK, Peti W, Page R. Three dimensional structure of the MqsR:MqsA complex: a novel TA pair comprised of a toxin homologous to RelE and an antitoxin with unique properties. PLoS Pathog [print-electronic]. 2009 Dec; 5(12): e1000706. PMID: 20041169, PMCID: PMC2791442, DOI: 10.1371/journal.ppat.1000706, ISSN: 1553-7374.
Brown BL, Hadley M, Page R. Heterologous high-level E. coli expression, purification and biophysical characterization of the spine-associated RapGAP (SPAR) PDZ domain. Protein Expr. Purif [print-electronic]. 2008 Nov; 62(1): 9-14. PMID: 18678258, PII: S1046-5928(08)00179-4, DOI: 10.1016/j.pep.2008.07.003, ISSN: 1096-0279.
Taylor JL, Ayres-Galhardo PH, Brown BL. Elucidating the Role of Human ALAS2 C-terminal Mutations Resulting in Loss of Function and Disease. Biochemistry [print-electronic]. 2024 Jul 7/2/2024; 63(13): 1636-46. PMID: 38888931, PMCID: PMC11223264, DOI: 10.1021/acs.biochem.4c00066, ISSN: 1520-4995.
Brown BL. Heterologous Expression and Purification of Eukaryotic ALA Synthase from E. coli. Methods Mol Biol. 2024; 2839: 233-41. PMID: 39008257, DOI: 10.1007/978-1-0716-4043-2_13, ISSN: 1940-6029.
Tran JU, Brown BL. The yeast ALA synthase C-terminus positively controls enzyme structure and function. Protein Sci. 2023 Apr; 32(4): e4600. PMID: 36807942, PMCID: PMC10031213, DOI: 10.1002/pro.4600, ISSN: 1469-896X.
Taylor JL, Brown BL. Structural basis for dysregulation of aminolevulinic acid synthase in human disease. J Biol Chem [print-electronic]. 2022 Mar; 298(3): 101643. PMID: 35093382, PMCID: PMC8892079, PII: S0021-9258(22)00083-7, DOI: 10.1016/j.jbc.2022.101643, ISSN: 1083-351X.
Tran JU, Brown BL. Structural Basis for Allostery in PLP-dependent Enzymes. Front Mol Biosci. 2022; 9: 884281. PMID: 35547395, PMCID: PMC9081730, PII: 884281, DOI: 10.3389/fmolb.2022.884281, ISSN: 2296-889X.
Brown BL, Iverson TM. Handling heme with care. Nat Chem Biol. 2021 Jul; 17(7): 751-2. PMID: 34103722, PII: 10.1038/s41589-021-00821-7, DOI: 10.1038/s41589-021-00821-7, ISSN: 1552-4469.
Hung LY, Tanaka Y, Herbine K, Pastore C, Singh B, Ferguson A, Vora N, Douglas B, Zullo K, Behrens EM, Li Hui Tan T, Kohanski MA, Bryce P, Lin C, Kambayashi T, Reed DR, Brown BL, Cohen NA, Herbert DR. Cellular context of IL-33 expression dictates impact on anti-helminth immunity. Sci Immunol. 2020 Nov 11/13/2020; 5(53): PMID: 33188058, PII: 5/53/eabc6259, DOI: 10.1126/sciimmunol.abc6259, ISSN: 2470-9468.
Brown BL, Vieux EF, Kalastavadi T, Kim S, Chen JZ, Baker TA. N domain of the Lon AAA+ protease controls assembly and substrate choice. Protein Sci [print-electronic]. 2018 Nov 11/21/2018; PMID: 30461098, DOI: 10.1002/pro.3553, ISSN: 1469-896X.
Brown BL, Kardon JR, Sauer RT, Baker TA. Structure of the Mitochondrial Aminolevulinic Acid Synthase, a Key Heme Biosynthetic Enzyme. Structure [print-electronic]. 2018 Apr 4/3/2018; 26(4): 580-589.e4. PMID: 29551290, PMCID: PMC5894356, PII: S0969-2126(18)30052-2, DOI: 10.1016/j.str.2018.02.012, ISSN: 1878-4186.
Davis JR, Brown BL, Page R, Sello JK. Study of PcaV from Streptomyces coelicolor yields new insights into ligand-responsive MarR family transcription factors. Nucleic Acids Res [print-electronic]. 2013 Apr 4/1/2013; 41(6): 3888-900. PMID: 23396446, PMCID: PMC3616709, PII: gkt009, DOI: 10.1093/nar/gkt009, ISSN: 1362-4962.
Brown BL, Lord DM, Grigoriu S, Peti W, Page R. The Escherichia coli toxin MqsR destabilizes the transcriptional repression complex formed between the antitoxin MqsA and the mqsRA operon promoter. J. Biol. Chem [print-electronic]. 2013 Jan 1/11/2013; 288(2): 1286-94. PMID: 23172222, PMCID: PMC3543012, PII: M112.421008, DOI: 10.1074/jbc.M112.421008, ISSN: 1083-351X.
Wang X, Kim Y, Hong SH, Ma Q, Brown BL, Pu M, Tarone AM, Benedik MJ, Peti W, Page R, Wood TK. Antitoxin MqsA helps mediate the bacterial general stress response. Nat. Chem. Biol [print-electronic]. 2011 Jun; 7(6): 359-66. PMID: 21516113, PMCID: PMC3097263, PII: nchembio.560, DOI: 10.1038/nchembio.560, ISSN: 1552-4469.
Brown BL, Wood TK, Peti W, Page R. Structure of the Escherichia coli antitoxin MqsA (YgiT/b3021) bound to its gene promoter reveals extensive domain rearrangements and the specificity of transcriptional regulation. J. Biol. Chem [print-electronic]. 2011 Jan 1/21/2011; 286(3): 2285-96. PMID: 21068382, PMCID: PMC3023523, PII: M110.172643, DOI: 10.1074/jbc.M110.172643, ISSN: 1083-351X.
Brown BL, Page R. Preliminary crystallographic analysis of the Escherichia coli antitoxin MqsA (YgiT/b3021) in complex with mqsRA promoter DNA. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun [print-electronic]. 2010 Sep 9/1/2010; 66(Pt 9): 1060-3. PMID: 20823526, PMCID: PMC2935227, PII: S1744309110028617, DOI: 10.1107/S1744309110028617, ISSN: 1744-3091.
Brown BL, Grigoriu S, Kim Y, Arruda JM, Davenport A, Wood TK, Peti W, Page R. Three dimensional structure of the MqsR:MqsA complex: a novel TA pair comprised of a toxin homologous to RelE and an antitoxin with unique properties. PLoS Pathog [print-electronic]. 2009 Dec; 5(12): e1000706. PMID: 20041169, PMCID: PMC2791442, DOI: 10.1371/journal.ppat.1000706, ISSN: 1553-7374.
Brown BL, Hadley M, Page R. Heterologous high-level E. coli expression, purification and biophysical characterization of the spine-associated RapGAP (SPAR) PDZ domain. Protein Expr. Purif [print-electronic]. 2008 Nov; 62(1): 9-14. PMID: 18678258, PII: S1046-5928(08)00179-4, DOI: 10.1016/j.pep.2008.07.003, ISSN: 1096-0279.