Structural biology of macromolecular aggregates

Ignasi Fita

Group Leader
Professor (IBMB-CSIC)
Office Tel : +34 93 40 34949

e-mail : ignasi.fitairbbarcelona.org

Background

During the last fifteen years our research has focused on the structure-function relationships of a diversity of proteins and macromolecular complexes directly involved in pathological processes. The systems studied, with over a hundred peer-reviewed publications, range from a number of small protein kinase domains to several intact RNA viruses and in complex with their cellular receptors. To perform our activities, we use mainly X-ray crystallography, often complemented with other techniques including, in particular, mass spectrometry and high resolution cryo-electron microscopy.

Research Interests

Our general goal is first to determine the three-dimensional organization of a number of molecular systems, and second, to use these data as a framework to examine the biochemical and biological processes in which these molecular systems participate. The development of methodologies required by some of these studies has also been an objective in itself.

Research Lines

At present our main lines of research are:

Enzymes related with Oxidative Stress
a) Mono-functional Catalases,
b) Bifunctional Catalases-Peroxidases,
c) Peroxidases (in particular mammalian peroxidases) and
d) Oxygenases.

Membrane bound proteins
a) Amino-acid transporters and
b) Virulence factors (in particular in Mycoplasmas)

Energetics of protein conformations

More info

• Fita Group Scientific Report 2009
• Fita Group Scientific Report 2008
• Fita Group Scientific Report 2007
• Fita Group Scientific Report 2005-2006

Structural biology of macromolecular aggregates

Performance of Molecular Mechanics Force Fields for RNA Simulations: Stability of UUCG and GNRA Hairpins
Banás P, Hollas D, Zgarbová Jurecka P, Orozco M, Cheatham TE, Sponer J and Otyepka M
J Chem Theory Comput, 6, 3836-3849 (2010)

The dynamic role of distal side residues in heme hydroperoxidase catalysis. Interplay between X-ray crystallography and ab initio MD simulations
Vidossich P, Alfonso-Prieto M, Carpena X, Fita I, Loewen PC and Rovira C
Arch Biochem Biophys, 500 (1), 37-44 (2010)

Substrate binding and catalysis in carbamate kinase ascertained by crystallographic and site-directed mutagenesis studies: movements and significance of a unique globular subdomain of this key enzyme for fermentative ATP production in bacteria
Ramón-Maiques S, Marina A, Guinot A, Gil-Ortiz F, Uriarte M, Fita I and Rubio V
J Mol Biol, 397 (5), 1261-1275 (2010)

Essential role of proximal histidine-asparagine interaction in mammalian peroxidases
Carpena X, Vidossich P, Schroettner K, Calisto BM, Banerjee S, Stampler J, Soudi M, Furtmüller PG, Rovira C, Fita I and Obinger C
J Biol Chem, 284 (38), 25929-25937 (2009)

The mechanism of vault opening from the high resolution structure of the N-terminal repeats of MVP
Querol-Audí J, Casañas A, Usón I, Luque D, Castón JR, Fita I and Verdaguer N
EMBO J, 28 (21), 3450-3457 (2009)

Aldo-keto reductases from the AKR1B subfamily: retinoid specificity and control of cellular retinoic acid levels
Ruiz FX, Gallego O, Ardèvol A, Moro A, Domínguez M, Alvarez S, Alvarez R, de Lera AR, Rovira C, Fita I, Parés X and Farrés J
Chem Biol Interact, 178 (1-3), 171-177 (2009)

Three-dimensional structure and enzymatic function of proapoptotic human p53-inducible quinone oxidoreductase PIG3
Porté S, Valencia E, Yakovtseva EA, Borràs E, Shafqat N, Debreczeny JE, Pike AC, Oppermann U, Farrés J, Fita I and Parés X
J Biol Chem, 284 (25), 17194-17205 (2009)

Structural and mechanistic insights into the association of PKCalpha-C2 domain to PtdIns(4,5)P2
Guerrero-Valero M, Ferrer-Orta C, Querol-Audí J, Marin-Vicente C, Fita I, Gómez-Fernández JC, Verdaguer N and Corbalán-García S
Proc Natl Acad Sci USA, 106 (16), 6603-6607 (2009)

Minor group human rhinovirus-receptor interactions: geometry of multimodular attachment and basis of recognition
Querol-Audí J, Konecsni T, Pous J, Carugo O, Fita I, Verdaguer N and Blaas D
FEBS Lett, 583 (1), 235-240 (2009)

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)

Structural and biochemical studies of TREX1 inhibition by metals. Identification of a new active histidine conserved in DEDDh exonucleases
Brucet M, Querol-Audí J, Bertlik K, Lloberas J, Fita I and Celada A
Protein Sci, 17 (12), 2059-2069 (2008)

Arginine and nitrogen storage
Llácer JL, Fita I and Rubio V
Curr Opin Struct Biol, 18 (6), 673-681 (2008)

Electronic state of the molecular oxygen released by catalase
Alfonso-Prieto M, Vidossich P, Rodríguez-Fortea A, Carpena X, Fita I, Loewen PC and Rovira C
J Phys Chem A, 112, 12843-12848 (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)

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)

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)

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)

Structural biology of macromolecular aggregates

Ignasi Fita
Group Leader
Professor (IBMB-CSIC)

Office Tel : +34 93 40 34949

e-mail : ignasi.fitairbbarcelona.org

Postdoctoral Fellows
Maria Mercè Ratera
tel +34 93 40 34700
e-mail: merce.raterairbbarcelona.org

Xavi Carpena
tel +34 93 40 34956
e-mail: xavier.carpenairbbarcelona.org

PhD Students
David Aparicio
tel +34 93 40 34956
e-mail: david.aparicioirbbarcelona.org

Luca Martinelli
tel +34 93 40 34956
e-mail: luca.martinelliirbbarcelona.org

Maria Adell
tel +34 93 40 34956
e-mail: maria.adellirbbarcelona.org

Lab Technicians
Mª Queralt García
tel +34 93 40 34956
e-mail: maria.garciairbbarcelona.org

Structural biology of macromolecular aggregates

• 11 April 2011
  Barcelona Visió
  X-Rays against the bacterium that causes tuberculosis
  
• 19 January 2011
  Investigación y Ciencia
  The common cold virus
  
• 14 April 2010
  El País
  Biological challenges for a synchrotron
  
• 26 October 2009
  Global Talent
  Vèncer la destresa del bacteri de la tuberculosi
  
• 19 October 2009
  Global Talent
  El IRB Barcelona participa en un proyecto europeo contra la tuberculosis