Biología estructural de los agregados macromoleculares
Ignasi Fita
Investigador Principal
Professor (IBMB-CSIC)
Tel Oficina : +34 93 403 49 49
correo-e : ignasi.fita
irbbarcelona.org
Introducción
Durante los últimos quince años, nuestro laboratorio ha estado trabajando en las relaciones estructura-función de una diversidad de proteínas y complejos macromoleculares que tienen una implicación directa en los procesos patológicos.
Los sistemas que se han estudiado durante estos años, con más de cien publicaciones en revistas científicas internacionales, abarcan desde un número de dominios pequeños de proteínas quinases hasta diversos virus de ARN intactos y los complejos con sus receptores celulares. La metodología estructural utilizada ha sido básicamente la cristalografía de rayos X, a menudo complementada con otras técnicas entre las cuales destacan la espectometría de masas y la crio-microscopia electrónica de alta resolución.
Áreas de interés científico
Los objetivos generales de nuestra investigación son, en primer lugar, la determinación de la organización en tres dimensiones de una serie de sistemas moleculares y, en segundo lugar, el uso de esta información como un marco para entender los procesos bioquímicos y biológicos en los cuales participan estos sistemas moleculares. Las herramientas metodológicas necesarias para algunos de estos estudios también constituyen un objetivo en sí mismos.
Líneas de Investigación
Actualmente, las principales líneas de investigación del grupo son:
Enzimas relacionados con el estrés oxidativo:
a) Catalasas monofuncionales,
b) Catalasas-Peroxidasas,
c) Peroxidasas (en especial las peroxidasas mamíferas), y
d) Oxigenasas
Proteínas de membranas:
a) Transportadores de aminoácidos, y
b) Factores de virulencia (en especial en los micoplasmas)
Energetics of protein conformations
Más información
Biología estructural de los agregados macromoleculares
RhaU of Rhizobium leguminosarum is a rhamnose mutarotase
Richardson SJ, Carpena X, Switala J, Perez-Luque R, Loewen PC and Oresnik IJ
J Bacteriol, 190 (8), 2903-2910 (2008)
Biosynthesis of isoprenoids in plants: structure of the 2C-methyl-D-erithrytol 2,4-cyclodiphosphate synthase from Arabidopsis thaliana. Comparison with the bacterial enzymes
Calisto BM, Perez-Gil J, Bergua M, Querol-Audi J, Fita I and Imperial S
Protein Sci, 16 (9), 2082-2088 (2007)
The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane
Fort J, de la Ballina LR, Burghardt HE, Ferrer-Costa C, Turnay J, Ferrer-Orta C, Usón I, Zorzano A, Fernández-Recio J, Orozco M, Lizarbe MA, Fita I and Palacín M
J Biol Chem, 282 (43), 31444-31452 (2007)
Versatility of the electronic structure of compound I in catalase-peroxidases
Vidossich P, Alfonso-Prieto M, Carpena X, Loewen PC, Fita I and Rovira C
J Am Chem Soc, 129 (44), 13436-13446 (2007)
Structure of the dimeric exonuclease TREX1 in complex with DNA displays a proline-rich binding site for WW Domains
Brucet M, Querol-Audí J, Serra M, Ramirez-Espain X, Bertlik K, Ruiz L, Lloberas J, Macias MJ, Fita I and Celada A
J Biol Chem, 282 (19), 14547-14557 (2007)
Two alternative substrate paths for compound I formation and reduction in catalase-peroxidase KatG from Burkholderia pseudomallei
Deemagarn T, Wiseman B, Carpena X, Ivancich A, Fita I and Loewen P
Proteins, 66 (1), 219-228 (2007)
Structural basis for the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10
Gallego O, Ruiz FX, Ardèvol A, Domínguez M, Alvarez R, de Lera AR, Rovira C, Farrés J, Fita I and Parés X
Proc Natl Acad Sci USA, 104 (52), 20764-20769 (2007)
A novel two-domain architecture within the amino acid kinase enzyme family revealed by the crystal structure of Escherichia coli glutamate 5-kinase
Marco-Marín C, Gil-Ortiz F, Pérez-Arellano I, Cervera J, Fita I and Rubio V
J Mol Biol, 367 (5), 1431-1446 (2007)
The structures and electronic configuration of compound I intermediates of Helicobacter pylori and Penicillium vitale catalases determined by X-ray crystallography and QM/MM density functional theory calculations
Alfonso-Prieto M, Borovik A, Carpena X, Murshudov G, Melik-Adamyan W, Fita I, Rovira C and Loewen PC
J Am Chem Soc, 129 (14), 4193-4205 (2007)
Structural and functional features of cinnamyl alcohol dehydrogenase (Adh6p) from Saccharomyces cerevisiae. Enzymology and molecular biology of carbonyl metabolism 13
Larroy C, Valencia E, Fita I, Pares X and Biosca A
Purdue University Press. West Lafayette Indiana (2007)
Combining experimental data for structure determination of flexible multimeric macromolecules by molecular replacement
Trapani S, Abergel C, Gutsche I, Horcajada C, Fita I and Navaza J
Acta Crystallogr D Biol Crystallogr, 62 (Pt 5), 467-475 (2006)
Structural bases of feed-back control of arginine biosynthesis, revealed by the structures of two hexameric N-acetylglutamate kinases, from Thermotoga maritima and Pseudomonas aeruginosa
Ramón-Maiques S, Fernández-Murga ML, Gil-Ortiz F, Vagin A, Fita I and Rubio V
J Mol Biol, 356 (3), 695-713 (2006)
Crystal structure of an archaeal glycogen synthase: insights into oligomerisation and substrate binding of eukaryotic glycogen synthases
Horcajada C, Guinovart JJ, Fita I and Ferrer JC
J Biol Chem, 281 (5), 2923-2931 (2006)
Roles for Arg426 and Trp111 in the modulation of NADH oxidase activity of the catalase-peroxidase KatG from Burkholderia pseudomallei inferred from pH-induced structural changes
Carpena X, Wiseman B, Deemagarn T, Herguedas B, Ivancich A, Singh R, Loewen PC and Fita I
Biochemistry, 45 (16), 5171-5179 (2006)
Structural characterization of the Ser324Thr variant of the catalase-peroxidase (KatG) from Burkholderia pseudomallei
Deemagarn T, Carpena X, Singh R, Wiseman B, Fita I and Loewen PC
J Mol Biol, 345 (1), 21-28 (2005)
A molecular switch and electronic circuit modulate catalase activity in catalase-peroxidases
Carpena X, Wiseman B, Deemagarn T, Singh R, Switala J, Ivancich A, Fita I and Loewen PC
EMBO Rep, 6 (12), 1156-1162 (2005)
Crystal structure of a putative type I restriction-modification S subunit from Mycoplasma genitalium
Calisto BM, Pich OQ, Piñol J, Fita I, Querol E and Carpena X
J Mol Biol, 351 (4), 749-762 (2005)
Characterization of a large subunit catalase truncated by proteolytic cleavage
Chelikani P, Carpena X, Pérez-Luque R, Donald LJ, Duckworth HW, Switala J, Fita I and Loewen PC
Biochemistry, 44 (15), 5597-5605 (2005)
X-ray crystallography of rhinovirus-receptor complexes
Querol J, Fita I and Verdaguer N
Crystallogr Rev, 11, 73-81 (2005)
Structural plasticity in alcohol dehydrogenase: How an NADP (H)-dependent enzyme becomes specific for NAD(H)
Rosell A, Valencia E, Borras E, Ochoa WF, Fita I, Pares X and Farres J
Enzymol Mol Biol Carbonyl Metab, 12, 181-189 (2005)
A first principles study of the binding of formic acid in catalase complementing high resolution X-ray structures
Rovira C, Alfonso-Prieto M, Biarnes X, Carpena X, Fita I and Loewen PC
Chem Phys, 323, 129-137 (2005)
Preliminary analysis of two and three dimensional crystals of vault ribonucleoprotein particles
Querol J, Perez-Luque R, Fita I, Lopez C, Gastón JR, Carrascosa JL and Verdaguer N
J Struct Biol, 151, 111-115 (2005)
Catalase-peroxidases (KatG) exhibit NADH oxidase activity
Singh R, Wiseman B, Deemagarn T, Donald LJ, Duckworth HW, Carpena X, Fita I and Loewen PC
J Biol Chem, 279 (41), 43098-43106 (2004)
X-ray structure of a minor group human rhinovirus bound to a fragment of its cellular receptor protein
Verdaguer N, Fita I, Reithmayer M, Moser R and Blaas D
Nat Struct Mol Biol, 11 (5), 429-434 (2004)
Apo and Holo structures of an NADPH-dependent cinnamyl alcohol dehydrogenase from Saccharomyces cerevisiae
Valencia E, Larroy C, Ochoa WF, Parés X, Fita I and Biosca JA
J Mol Biol, 341 (4), 1049-1062 (2004)
Structure of swine vesicular disease virus: mapping of changes occurring during adaptation of human coxsackie B5 virus to infect swine
Verdaguer N, Jimenez-Clavero MA, Fita I and Ley V
J Virol, 77 (18), 9780-9789 (2003)
Characterization of the catalase-peroxidase KatG from Burkholderia pseudomallei by mass spectrometry
Donald LJ, Krokhin OV, Duckworth HW, Wiseman B, Deemagarn T, Singh R, Switala J, Carpena X, Fita I and Loewen PC
J Biol Chem, 278 (37), 35687-35692 (2003)
Complete reversal of coenzyme specificity by concerted mutation of three consecutive residues in alcohol dehydrogenase
Rosell A, Valencia E, Ochoa WF, Fita I, Pares X and Farres J
J Biol Chem, 278 (42), 40573-40580 (2003)
Catalase-peroxidase KatG of Burkholderia pseudomallei at 1.7A resolution
Carpena X, Loprasert S, Mongkolsuk S, Switala J, Loewen PC and Fita I
J Mol Biol, 327 (2), 475-489 (2003)
Crystal structure of the vertebrate NADP(H)-dependent alcohol dehydrogenase (ADH8)
Rosell A, Valencia E, Parés X, Fita I, Farrés J and Ochoa WF
J Mol Biol, 330 (1), 75-85 (2003)
The course of phosphorus in the reaction of N-acetyl-L-glutamate kinase, determined from the structures of crystalline complexes, including a complex with an AlF(4)(-) transition state mimic
Gil-Ortiz F, Ramón-Maiques S, Fita I and Rubio V
J Mol Biol, 331 (1), 231-244 (2003)
An electrical potential in the access channel of catalases enhances catalysis
Chelikani P, Carpena X, Fita I and Loewen PC
J Biol Chem, 278 (33), 31290-31296 (2003)
