Biologia estructural dels agregats macromoleculars
Ignasi Fita
Investigador Principal
Professor (IBMB-CSIC)
Tel Oficina : +34 93 403 49 49
correu-e : ignasi.fita
irbbarcelona.org
Introducció
Durant els darrers quinze anys, el nostre laboratori ha estat treballant en les relacions estructura-funció d’una diversitat de proteïnes i complexos macromoleculars que tenen una implicació directa en els processos patològics.
Els sistemes que s’han estudiat durant aquests anys, amb més de cent publicacions en revistes científiques internacionals, abarquen des d’un nombre de dominis petits de proteïnes quinases fins a diversos virus d’ARN intactes i els complexes amb els seus receptors cel·lulars. La metodologia estructural utilitzada ha estat bàsicament la cristal·lografia de raigs X, sovint complementada amb d’altres tècniques, entre les quals destaquen, l’espectometria de masses i la crio-microcospia electrònica d’alta resolució.
Camps d'Investigació
Els objectius generals de la nostra recerca són, en primer lloc, la determinació de l’organització en tres dimensions d’un seguit de sistemes moleculars i, en segon lloc, l’ús d’aquesta informació com a marc per a entendre els processos bioquímics i biològics en els quals participen aquests sistemes moleculars.
Les eines metodològiques necessàries per a alguns d’aquests estudis també constitueixen un objectiu en sí mateix.
Línies de Recerca
Actualment, les principals línies de recerca del grup són:
Enzims relacionats amb estrès oxidatiu:
a) Catalases monofuncionals,
b) Catalases-Peroxidases,
c) Peroxidases (en especial les peroxidases mamífers), i
d) Oxigenases
Proteïnes de membranes:
a) Transportadors d’aminoàcids, i
b) Factors de virulència (en especial en els micoplasmes)
Energetics of protein conformations
Més informació
Biologia estructural dels agregats macromoleculars
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)
