GloriaFerreira

Gloria Ferreira, Ph.D.

Professor, College Of Medicine Molecular Medicine

College Of Medicine Molecular Medicine

Professor, Department of Molecular Medicine, College of Medicine, University of South Florida

Affiliated Professor, Department of Chemistry, University of South Florida

Member, Florida Center of Excellence for Biomolecular Identification and Targeted Therapeutics (FCoE-BITT), University of South Florida

Contact Info 12901 Bruce B. Downs Blvd.
MDC 7
Tampa, FL 33612

Academic Email: gferreir@health.usf.edu

Academic Phone: (813) 974-5797

View My C.V.

Education

  • PHD, Biochemistry, University Of Georgia, 1986

Interdisciplinary and Emerging Signature Programs

  • Cancer Biology
  • Cardiovascular

Research Interests

  • 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.

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)

Recent Publications

  • Hunter, GA.Ferreira, GC. Molecular enzymology of 5-Aminolevulinate synthase, the gatekeeper of heme biosynthesis. Biochimica et biophysica acta. , 2011. http://www.ncbi.nlm.nih.gov/pubmed/21215825
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/20194506
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/20966079
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/19562746
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/19268008
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/18423489
  • Hunter, GA.Sampson, MP.Ferreira, GC. Metal ion substrate inhibition of ferrochelatase. The Journal of biological chemistry. 283(35) : 23685-91, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18593702
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/17485466
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/17469798
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/16371422
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/16905545
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/16469498
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/16503645
  • Shi, Z.Ferreira, GC. Modulation of inhibition of ferrochelatase by N-methylprotoporphyrin. The Biochemical journal. 399(1) : 21-8, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16792525
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/15641778
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/15496139
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/15840827
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/15850552
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/16211492
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/14981080
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/12732649
  • Hofer, T.Wenger, RH.Kramer, MF.Ferreira, GC.Gassmann, M. Hypoxic up-regulation of erythroid 5-aminolevulinate synthase. Blood. 101(1) : 348-50, 2003. http://www.ncbi.nlm.nih.gov/pubmed/12393745
  • Shi, Z.Ferreira, GC. A continuous anaerobic fluorimetric assay for ferrochelatase by monitoring porphyrin disappearance. Analytical biochemistry. 318(1) : 18-24, 2003. http://www.ncbi.nlm.nih.gov/pubmed/12782026
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/12736261
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/12191993
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/11929042
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/12699240
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/11939775
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/12081474
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/11279050
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/11336654
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/11566198
  • Kramer, MF.Gunaratne, P.Ferreira, GC. Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene. Gene. 247(1-2) : 153-66, 2000. http://www.ncbi.nlm.nih.gov/pubmed/10773455
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/10942404
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/10704201
  • Ferreira, GC. Ferrochelatase. The international journal of biochemistry & cell biology. 31(10) : 995-1000, 1999. http://www.ncbi.nlm.nih.gov/pubmed/10582332
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/10493823
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/10212188
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/10090759
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/9484217
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/9521672
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/9605326
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/8916896
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/8688429
  • Ferreira, GC. Heme biosynthesis: biochemistry, molecular biology, and relationship to disease. Journal of bioenergetics and biomembranes. 27(2) : 147-50, 1995. http://www.ncbi.nlm.nih.gov/pubmed/7592561
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/7663334
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/7575558
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/7849027
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/7592569
  • Ferreira, GC.Gong, J. 5-Aminolevulinate synthase and the first step of heme biosynthesis. Journal of bioenergetics and biomembranes. 27(2) : 151-9, 1995. http://www.ncbi.nlm.nih.gov/pubmed/7592562
  • Hunter, GA.Ferreira, GC. A continuous spectrophotometric assay for 5-aminolevulinate synthase that utilizes substrate cycling. Analytical biochemistry. 226(2) : 221-4, 1995. http://www.ncbi.nlm.nih.gov/pubmed/7793621
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/7592847
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/8125912
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/8308010
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/8168843
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/8268805
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/8132488
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/8416963
  • Ferreira, GC. Erythroid 5-aminolevulinate synthase and X-linked sideroblastic anemia. The Journal of the Florida Medical Association. 80(7) : 481-3, 1993. http://www.ncbi.nlm.nih.gov/pubmed/8089650
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/1531983
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/1985946
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/2250020
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/2670944
  • Ferreira, GC.Dailey, HA. Mouse protoporphyrinogen oxidase. Kinetic parameters and demonstration of inhibition by bilirubin. The Biochemical journal. 250(2) : 597-603, 1988. http://www.ncbi.nlm.nih.gov/pubmed/2451512
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/3346226
  • 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. http://www.ncbi.nlm.nih.gov/pubmed/3558411
  • Rigler, MW.Ferreira, GC.Patton, JS. Intramembranous particles are clustered on microvillus membrane vesicles. Biochimica et biophysica acta. 816(1) : 131-41, 1985. http://www.ncbi.nlm.nih.gov/pubmed/4005232

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)