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Gloria Ferreira, Ph.D.
Member, Florida Center of Excellence for Biomolecular Identification and Targeted Therapeutics (FCoE-BITT)
Affiliated Professor, Department of Chemistry
Professor, Department of Molecular Medicine, College of Medicine

Primary Department: COLLEGE OF MEDICINE MOLECULAR MEDICINE

Professor
COLLEGE OF MEDICINE MOLECULAR MEDICINE

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Contacts
Email: gferreir@health.usf.edu
Phone: (813) 974-5797
Office: MDC, 2152
Mailing address 12901 Bruce B. Downs Blvd. MDC 7
Tampa, FL 33612
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Education
  • PHD, Biochemistry, University Of Georgia, Athens, United States - 1986.
  •  
    Interdisciplinary & Emerging Signature Programs
    Cancer Biology, Cardiovascular.
     
    Research Summary

    Our main research interest is defining the reaction and regulatory mechanisms of the first and terminal heme biosynthetic pathway enzymes, 5-aminolevulinate synthase (ALAS) and ferrochelatase (FC). Iron overload is a clinically important feature of sideroblastic anemia, X-linked SA, and myelodysplastic syndrome, which often results from either ineffective hematopoiesis or the repeated transfusions undergone by the patients to manage their erythropoietic defects. The pathological consequences of mitochondrial mishandling of iron and heme synthesis are also evident in erythropoietic porphyrias. There is no cure for the above disorders, and thus understanding the mechanisms of the terminal stages of erythropoiesis becomes necessary for discovering novel therapeutic targets. Towards this goal, our on-going research focuses on establishing 1) whether succinyl-CoA synthetase b-subunit allosterically fine-tunes the activity of erythroid ALAS and 2) the mechanism of Fe2+ delivery to FC.

     
    Links

    Lab Link:  


    Selected Publications
  • Hunter GA, Ferreira GC. Molecular enzymology of 5-Aminolevulinate synthase, the gatekeeper of heme biosynthesis. Biochimica et biophysica acta. : , 2011.
  • Lendrihas T, Hunter GA, Ferreira GC. Targeting the active site gate to yield hyperactive variants of 5-aminolevulinate synthase. The Journal of biological chemistry. 285(18) : 13704-11, 2010.
  • Hunter GA, Ferreira GC. Identification and characterization of an inhibitory metal ion-binding site in ferrochelatase. The Journal of biological chemistry. 285(53) : 41836-42, 2010.
  • Lendrihas T, Zhang J, Hunter GA, Ferreira GC. Arg-85 and Thr-430 in murine 5-aminolevulinate synthase coordinate acyl-CoA-binding and contribute to substrate specificity. Protein science : a publication of the Protein Society. 18(9) : 1847-59, 2009.
  • Hunter GA, Ferreira GC. 5-aminolevulinate synthase: catalysis of the first step of heme biosynthesis. Cellular and molecular biology (Noisy-le-Grand, France). 55(1) : 102-10, 2009.
  • Karlberg T, Hansson MD, Yengo RK, Johansson R, Thorvaldsen HO, Ferreira GC, Hansson M, Al-Karadaghi S. Porphyrin binding and distortion and substrate specificity in the ferrochelatase reaction: the role of active site residues. Journal of molecular biology. 378(5) : 1074-83, 2008.
  • Hunter GA, Sampson MP, Ferreira GC. Metal ion substrate inhibition of ferrochelatase. The Journal of biological chemistry. 283(35) : 23685-91, 2008.
  • Hunter GA, Zhang J, Ferreira GC. Transient kinetic studies support refinements to the chemical and kinetic mechanisms of aminolevulinate synthase. The Journal of biological chemistry. 282(32) : 23025-35, 2007.
  • Turbeville TD, Zhang J, Hunter GA, Ferreira GC. Histidine 282 in 5-aminolevulinate synthase affects substrate binding and catalysis. Biochemistry. 46(20) : 5972-81, 2007.
  • Gakh O, Park S, Liu G, Macomber L, Imlay JA, Ferreira GC, Isaya G. Mitochondrial iron detoxification is a primary function of frataxin that limits oxidative damage and preserves cell longevity. Human molecular genetics. 15(3) : 467-79, 2006.
  • Dias JS, Macedo AL, Ferreira GC, Peterson FC, Volkman BF, Goodfellow BJ. The first structure from the SOUL/HBP family of heme-binding proteins, murine P22HBP. The Journal of biological chemistry. 281(42) : 31553-61, 2006.
  • Al-Karadaghi S, Franco R, Hansson M, Shelnutt JA, Isaya G, Ferreira GC. Chelatases: distort to select? Trends in biochemical sciences. 31(3) : 135-42, 2006.
  • Shi Z, Franco R, Haddad R, Shelnutt JA, Ferreira GC. The conserved active-site loop residues of ferrochelatase induce porphyrin conformational changes necessary for catalysis. Biochemistry. 45(9) : 2904-12, 2006.
  • Shi Z, Ferreira GC. Modulation of inhibition of ferrochelatase by N-methylprotoporphyrin. The Biochemical journal. 399(1) : 21-8, 2006.
  • Shipovskov, S., Karlberg, T., Fodje, M., Hansson, M. D., Ferreira, G. C, Hansson, M., Reimann, C. T. and Al-Karadaghi, S. Ferrochelatase-catalyzed Metallation of the Transition-state Inhibitor N-methyl Mesoporphyrin: A Time-resolved Crystallographic and Mass Spectrometric Study. Journal of Molecular Biololgy. 352: 1081-1090, 2005.
  • O'Neill HA, Gakh O, Park S, Cui J, Mooney SM, Sampson M, Ferreira GC, Isaya G. Assembly of human frataxin is a mechanism for detoxifying redox-active iron. Biochemistry. 44(2) : 537-45, 2005.
  • Franco R, Bai G, Prosinecki V, Abrunhosa F, Ferreira GC, Bastos M. Porphyrin-substrate binding to murine ferrochelatase: effect on the thermal stability of the enzyme. The Biochemical journal. 386(Pt 3) : 599-605, 2005.
  • Zhang J, Cheltsov AV, Ferreira GC. Conversion of 5-aminolevulinate synthase into a more active enzyme by linking the two subunits: spectroscopic and kinetic properties. Protein science : a publication of the Protein Society. 14(5) : 1190-200, 2005.
  • Hunter GA, Rivera E, Ferreira GC. Supraphysiological concentrations of 5-aminolevulinic acid dimerize in solution to produce superoxide radical anions via a protonated dihydropyrazine intermediate. Archives of biochemistry and biophysics. 437(2) : 128-37, 2005.
  • Dias JS, Macedo AL, Ferreira GC, Jeanty N, Taketani S, Goodfellow BJ, Peterson FC, Volkman BF. 1H, 15N and 13C resonance assignments of the heme-binding protein murine p22HBP. Journal of biomolecular NMR. 32(4) : 338, 2005.
  • Shi Z, Ferreira GC. Probing the active site loop motif of murine ferrochelatase by random mutagenesis. The Journal of biological chemistry. 279(19) : 19977-86, 2004.
  • Ferreira, G. C. Heme Synthesis Encyclopedia of Biological Chemistry. ((Lennarz, W. and Lane, M. D., Eds.), Academic Press, San Diego, CA, USA.) : 2:362-2:366, 2004.
  • Park S, Gakh O, O'Neill HA, Mangravita A, Nichol H, Ferreira GC, Isaya G. Yeast frataxin sequentially chaperones and stores iron by coupling protein assembly with iron oxidation. The Journal of biological chemistry. 278(33) : 31340-51, 2003.
  • Hofer T, Wenger RH, Kramer MF, Ferreira GC, Gassmann M. Hypoxic up-regulation of erythroid 5-aminolevulinate synthase. Blood. 101(1) : 348-50, 2003.
  • Shi Z, Ferreira GC. A continuous anaerobic fluorimetric assay for ferrochelatase by monitoring porphyrin disappearance. Analytical biochemistry. 318(1) : 18-24, 2003.
  • Cheltsov AV, Guida WC, Ferreira GC. Circular permutation of 5-aminolevulinate synthase: effect on folding, conformational stability, and structure. The Journal of biological chemistry. 278(30) : 27945-55, 2003.
  • Krishnamachary, B., Berg-Dixon, S., Kelly, B., Agani, F., Feldser, D., Ferreira, G., Iyer, N., LaRusch, J., Pak, B., Taghavi, P., and Semenza, G. L. Regulation of Colon Carcinoma Cell Invasion by Hypoxia-inducible Factor 1. Cancer Res.. 63: 1138-1143, 2003.
  • Zhang J, Ferreira GC. Transient state kinetic investigation of 5-aminolevulinate synthase reaction mechanism. The Journal of biological chemistry. 277(47) : 44660-9, 2002.
  • Ferreira GC, Cheltsov AV. Circular permutation of 5-aminolevulinate synthase as a tool to evaluate folding, structure and function. Cellular and molecular biology (Noisy-le-Grand, France). 48(1) : 11-6, 2002.
  • Ferreira GC, Zhang JS. Mechanism of 5-aminolevulinate synthase and the role of the protein environment in controlling the cofactor chemistry. Cellular and molecular biology (Noisy-le-Grand, France). 48(8) : 827-33, 2002.
  • Ferreira GC, Franco R, Mangravita A, George GN. Unraveling the substrate-metal binding site of ferrochelatase: an X-ray absorption spectroscopic study. Biochemistry. 41(15) : 4809-18, 2002.
  • Lu Y, Sousa A, Franco R, Mangravita A, Ferreira GC, Moura I, Shelnutt JA. Binding of protoporphyrin IX and metal derivatives to the active site of wild-type mouse ferrochelatase at low porphyrin-to-protein ratios. Biochemistry. 41(26) : 8253-62, 2002.
  • Cheltsov AV, Barber MJ, Ferreira GC. Circular permutation of 5-aminolevulinate synthase. Mapping the polypeptide chain to its function. The Journal of biological chemistry. 276(22) : 19141-9, 2001.
  • Franco R, Pereira AS, Tavares P, Mangravita A, Barber MJ, Moura I, Ferreira GC. Substitution of murine ferrochelatase glutamate-287 with glutamine or alanine leads to porphyrin substrate-bound variants. The Biochemical journal. 356(Pt 1) : 217-22, 2001.
  • Goodfellow BJ, Dias JS, Ferreira GC, Henklein P, Wray V, Macedo AL. The solution structure and heme binding of the presequence of murine 5-aminolevulinate synthase. FEBS letters. 505(2) : 325-31, 2001.
  • Kramer MF, Gunaratne P, Ferreira GC. Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene. Gene. 247(1-2) : 153-66, 2000.
  • Schneider-Yin X, Gouya L, Dorsey M, Rüfenacht U, Deybach JC, Ferreira GC. Mutations in the iron-sulfur cluster ligands of the human ferrochelatase lead to erythropoietic protoporphyria. Blood. 96(4) : 1545-9, 2000.
  • Franco R, Ma JG, Lu Y, Ferreira GC, Shelnutt JA. Porphyrin interactions with wild-type and mutant mouse ferrochelatase. Biochemistry. 39(10) : 2517-29, 2000.
  • Ferreira GC. Ferrochelatase. The international journal of biochemistry & cell biology. 31(10) : 995-1000, 1999.
  • Hunter GA, Ferreira GC. Lysine-313 of 5-Aminolevulinate Synthase Acts as a General Base during Formation of the Quinonoid Reaction Intermediates. Biochemistry. 38(38) : 12526, 1999.
  • Feldser, D., Agani, F., Iyer, N. V., Pak, B., Ferreira, G., and Semenza, G. L. Reciprocal Positive Regulation of Hypoxia-inducible Factor 1 and Insulin-like Growth Factor 2. Cancer Res.. 59: 3915-3918, 1999.
  • Hunter GA, Ferreira GC. Pre-steady-state reaction of 5-aminolevulinate synthase. Evidence for a rate-determining product release. The Journal of biological chemistry. 274(18) : 12222-8, 1999.
  • Hunter GA, Ferreira GC. Lysine-313 of 5-aminolevulinate synthase acts as a general base during formation of the quinonoid reaction intermediates. Biochemistry. 38(12) : 3711-8, 1999.
  • Tan D, Harrison T, Hunter GA, Ferreira GC. Role of arginine 439 in substrate binding of 5-aminolevulinate synthase. Biochemistry. 37(6) : 1478-84, 1998.
  • Gong J, Hunter GA, Ferreira GC. Aspartate-279 in aminolevulinate synthase affects enzyme catalysis through enhancing the function of the pyridoxal 5'-phosphate cofactor. Biochemistry. 37(10) : 3509-17, 1998.
  • Tan D, Barber MJ, Ferreira GC. The role of tyrosine 121 in cofactor binding of 5-aminolevulinate synthase. Protein science : a publication of the Protein Society. 7(5) : 1208-13, 1998.
  • Gong J, Kay CJ, Barber MJ, Ferreira GC. Mutations at a glycine loop in aminolevulinate synthase affect pyridoxal phosphate cofactor binding and catalysis. Biochemistry. 35(45) : 14109-17, 1996.
  • Tan D, Ferreira GC. Active site of 5-aminolevulinate synthase resides at the subunit interface. Evidence from in vivo heterodimer formation. Biochemistry. 35(27) : 8934-41, 1996.
  • Ferreira GC. Heme biosynthesis: biochemistry, molecular biology, and relationship to disease. Journal of bioenergetics and biomembranes. 27(2) : 147-50, 1995.
  • Ferreira GC, Vajapey U, Hafez O, Hunter GA, Barber MJ. Aminolevulinate synthase: lysine 313 is not essential for binding the pyridoxal phosphate cofactor but is essential for catalysis. Protein science : a publication of the Protein Society. 4(5) : 1001-6, 1995.
  • Ferreira GC. Ferrochelatase binds the iron-responsive element present in the erythroid 5-aminolevulinate synthase mRNA. Biochemical and biophysical research communications. 214(3) : 875-8, 1995.
  • Gong J, Ferreira GC. Aminolevulinate synthase: functionally important residues at a glycine loop, a putative pyridoxal phosphate cofactor-binding site. Biochemistry. 34(5) : 1678-85, 1995.
  • Ferreira GC, Franco R, Lloyd SG, Moura I, Moura JJ, Huynh BH. Structure and function of ferrochelatase. Journal of bioenergetics and biomembranes. 27(2) : 221-9, 1995.
  • Ferreira GC, Gong J. 5-Aminolevulinate synthase and the first step of heme biosynthesis. Journal of bioenergetics and biomembranes. 27(2) : 151-9, 1995.
  • Hunter GA, Ferreira GC. A continuous spectrophotometric assay for 5-aminolevulinate synthase that utilizes substrate cycling. Analytical biochemistry. 226(2) : 221-4, 1995.
  • Franco R, Moura JJ, Moura I, Lloyd SG, Huynh BH, Forbes WS, Ferreira GC. Characterization of the iron-binding site in mammalian ferrochelatase by kinetic and Mössbauer methods. The Journal of biological chemistry. 270(44) : 26352-7, 1995.
  • Ferreira GC, Franco R, Lloyd SG, Pereira AS, Moura I, Moura JJ, Huynh BH. Mammalian ferrochelatase, a new addition to the metalloenzyme family. The Journal of biological chemistry. 269(10) : 7062-5, 1994.
  • Ferreira GC. Mammalian ferrochelatase. Overexpression in Escherichia coli as a soluble protein, purification and characterization. The Journal of biological chemistry. 269(6) : 4396-400, 1994.
  • Jabs EW, Thomas PJ, Bernstein M, Coss C, Ferreira GC, Pedersen PL. Chromosomal localization of genes required for the terminal steps of oxidative metabolism: alpha and gamma subunits of ATP synthase and the phosphate carrier. Human genetics. 93(5) : 600-2, 1994.
  • Ferreira GC, Neame PJ, Dailey HA. Heme biosynthesis in mammalian systems: evidence of a Schiff base linkage between the pyridoxal 5'-phosphate cofactor and a lysine residue in 5-aminolevulinate synthase. Protein science : a publication of the Protein Society. 2(11) : 1959-65, 1993.
  • Ferreira GC, Pedersen PL. Phosphate transport in mitochondria: past accomplishments, present problems, and future challenges. Journal of bioenergetics and biomembranes. 25(5) : 483-92, 1993.
  • Ferreira GC, Dailey HA. Expression of mammalian 5-aminolevulinate synthase in Escherichia coli. Overproduction, purification, and characterization. The Journal of biological chemistry. 268(1) : 584-90, 1993.
  • Ferreira GC. Erythroid 5-aminolevulinate synthase and X-linked sideroblastic anemia. The Journal of the Florida Medical Association. 80(7) : 481-3, 1993.
  • Ferreira GC, Pedersen PL. Overexpression of higher eukaryotic membrane proteins in bacteria. Novel insights obtained with the liver mitochondrial proton/phosphate symporter. The Journal of biological chemistry. 267(8) : 5460-6, 1992.
  • Pratt RD, Ferreira GC, Pedersen PL. Mitochondrial phosphate transport. Import of the H+/Pi symporter and role of the presequence. The Journal of biological chemistry. 266(2) : 1276-80, 1991.
  • Ferreira GC, Pratt RD, Pedersen PL. Mitochondrial proton/phosphate transporter. An antibody directed against the COOH terminus and proteolytic cleavage experiments provides new insights about its membrane topology. The Journal of biological chemistry. 265(34) : 21202-6, 1990.
  • Ferreira GC, Pratt RD, Pedersen PL. Energy-linked anion transport. Cloning, sequencing, and characterization of a full length cDNA encoding the rat liver mitochondrial proton/phosphate symporter. The Journal of biological chemistry. 264(26) : 15628-33, 1989.
  • Ferreira GC, Dailey HA. Mouse protoporphyrinogen oxidase. Kinetic parameters and demonstration of inhibition by bilirubin. The Biochemical journal. 250(2) : 597-603, 1988.
  • Ferreira GC, Andrew TL, Karr SW, Dailey HA. Organization of the terminal two enzymes of the heme biosynthetic pathway. Orientation of protoporphyrinogen oxidase and evidence for a membrane complex. The Journal of biological chemistry. 263(8) : 3835-9, 1988.
  • Ferreira GC, Dailey HA. Reconstitution of the two terminal enzymes of the heme biosynthetic pathway into phospholipid vesicles. The Journal of biological chemistry. 262(9) : 4407-12, 1987.
  • Rigler MW, Ferreira GC, Patton JS. Intramembranous particles are clustered on microvillus membrane vesicles. Biochimica et biophysica acta. 816(1) : 131-41, 1985.

  • Positions Held


    Memberships
  • American Society for Biochemistry and Molecular Biology (Member, 2007 - Present)
  • Biophysical Society (Member, 2007 - Present)
  • Protein Society (Member, 2007 - Present)
  • American Association for Advancement of Science (Member, 2007 - Present)
  • Sociedade Portuguesa de Bioquimica (Member, 2007 - Present)
  • American Society for Hematology (Member, 2007 - Present)
  • American Porphyria Foundation (Member, 2007 - Present)
  • Society of Porphyrins & Phatlocyanines (Member, 2007 - Present)
  • American Chemical Society (Member, 2007 - Present)


  • Awards/Honors
  • Elected Member (Nominating Committee of the Division of Biological Chemistry, American Chemical Society 2002 - 2004)
  • Elected Vice-Chair (Year 2000) and Chair (Year 2002) (Gordon Research Conference, The Chemistry and Biology of Tetrapyrroles - 2000)
  • National Science Foundation Young Investigator Award (1992 - 1997)
  • Presidential Young Faculty Award (University of South Florida 1995 - 1996)


  • Profile last modified on 07/07/2014