Search

Your search keyword '"Rovira, Carme"' showing total 704 results
Start Over Author "Rovira, Carme"
704 results on '"Rovira, Carme"'

1. The need to implement FAIR principles in biomolecular simulations

Author

Amaro, Rommie, Åqvist, Johan, Bahar, Ivet, Battistini, Federica, Bellaiche, Adam, Beltran, Daniel, Biggin, Philip C., Bonomi, Massimiliano, Bowman, Gregory R., Bryce, Richard, Bussi, Giovanni, Carloni, Paolo, Case, David, Cavalli, Andrea, Chang, Chie-En A., Cheatham III, Thomas E., Cheung, Margaret S., Chipot, Cris, Chong, Lillian T., Choudhary, Preeti, Cisneros, Gerardo Andres, Clementi, Cecilia, Collepardo-Guevara, Rosana, Coveney, Peter, Covino, Roberto, Crawford, T. Daniel, Peraro, Matteo Dal, de Groot, Bert, Delemotte, Lucie, De Vivo, Marco, Essex, Jonathan, Fraternali, Franca, Gao, Jiali, Gelpí, Josep Lluís, Gervasio, Francesco Luigi, Gonzalez-Nilo, Fernando Danilo, Grubmüller, Helmut, Guenza, Marina, Guzman, Horacio V., Harris, Sarah, Head-Gordon, Teresa, Hernandez, Rigoberto, Hospital, Adam, Huang, Niu, Huang, Xuhui, Hummer, Gerhard, Iglesias-Fernández, Javier, Jensen, Jan H., Jha, Shantenu, Jiao, Wanting, Jorgensen, William L., Kamerlin, Shina Caroline Lynn, Khalid, Syma, Laughton, Charles, Levitt, Michael, Limongelli, Vittorio, Lindahl, Erik, Lindorff-Larsen, Kresten, Loverde, Sharon, Lundborg, Magnus, Luo, Yun Lyna, Luque, Francisco Javier, Lynch, Charlotte I., MacKerell, Alexander, Magistrato, Alessandra, Marrink, Siewert J., Martin, Hugh, McCammon, J. Andrew, Merz, Kenneth, Moliner, Vicent, Mulholland, Adrian, Murad, Sohail, Naganathan, Athi N., Nangia, Shikha, Noe, Frank, Noy, Agnes, Oláh, Julianna, O'Mara, Megan, Ondrechen, Mary Jo, Onuchic, José N., Onufriev, Alexey, Osuna, Silvia, Panchenko, Anna R., Pantano, Sergio, Parish, Carol, Parrinello, Michele, Perez, Alberto, Perez-Acle, Tomas, Perilla, Juan R., Pettitt, B. Montgomery, Pietropalo, Adriana, Piquemal, Jean-Philip, Poma, Adolfo, Praprotnik, Matej, Ramos, Maria J., Ren, Pengyu, Reuter, Nathalie, Roitberg, Adrian, Rosta, Edina, Rovira, Carme, Roux, Benoit, Röthlisberger, Ursula, Sanbonmatsu, Karissa Y., Schlick, Tamar, Shaytan, Alexey K., Simmerling, Carlos, Smith, Jeremy C., Sugita, Yuji, Świderek, Katarzyna, Taiji, Makoto, Tao, Peng, Tikhonova, Irina G., Tirado-Rives, Julian, Tunón, Inaki, Van Der Kamp, Marc W., Van der Spoel, David, Velankar, Sameer, Voth, Gregory A., Wade, Rebecca, Warshel, Ariel, Welborn, Valerie Vaissier, Wetmore, Stacey, Wong, Chung F., Yang, Lee-Wei, Zacharias, Martin, and Orozco, Modesto

Subjects
Quantitative Biology - Biomolecules
Abstract

This letter illustrates the opinion of the molecular dynamics (MD) community on the need to adopt a new FAIR paradigm for the use of molecular simulations. It highlights the necessity of a collaborative effort to create, establish, and sustain a database that allows findability, accessibility, interoperability, and reusability of molecular dynamics simulation data. Such a development would democratize the field and significantly improve the impact of MD simulations on life science research. This will transform our working paradigm, pushing the field to a new frontier. We invite you to support our initiative at the MDDB community (https://mddbr.eu/community/)

Published
2024

11. Formation of a Covalent Adduct in Retaining β‐Kdo Glycosyl‐Transferase WbbB via Substrate‐Mediated Proton Relay.

Author

Sagiroglugil, Mert, Liao, Qinghua, Planas, Antoni, and Rovira, Carme

Subjects
CHEMICAL reactions, STEREOCHEMISTRY, MOLECULAR dynamics, SACCHARIDES, CRYSTAL structure
Abstract

The GT99 domain of the membrane‐anchored WbbB glycosyltransferase (WbbBGT99) catalyzes the transfer of 3‐deoxy‐D‐manno‐oct‐2‐acid (β‐Kdo) to an O‐antigen saccharide acceptor with retention of stereochemistry. It has been proposed that the enzyme follows an unprecedented double‐displacement mechanism involving the formation of covalent adduct between the Kdo sugar and an active site residue (Asp232) that is properly oriented for nucleophilic attack. Here we use QM/MM metadynamics simulations on recently reported crystal structures to provide theoretical evidence for the formation of such adduct and unveil the atomic details of the chemical reaction. Our results support the interpretation made on the basis of X‐ray and mass spectrometry analyses. Moreover, we show that the formation of the β‐Kdo‐Asp232 adduct is assisted by the sugar Kdo‐carboxylate group, which mediates the transfer of a proton from Asp232 towards the phosphate leaving group, alleviating electrostatic repulsion between the two negatively charged carboxylate groups. The computed mechanism also explains why His265, previously proposed to act as a general acid, does not impair catalysis. This mechanism can be extended to other related enzymes, expanding the repertoire of GT mechanisms in Nature. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

12. Constrained Catalytic Itinerary of a Retaining 3,6‐Anhydro‐D‐Galactosidase, a Key Enzyme in Red Algal Cell Wall Degradation.

Author

Wallace, Michael D., Cuxart, Irene, Roret, Thomas, Guée, Laura, Debowski, Aleksandra W., Czjzek, Mirjam, Rovira, Carme, Stubbs, Keith A., and Ficko‐Blean, Elizabeth

Subjects
ALGAL cells, POLYSACCHARIDES, ERYTHROCYTES, BIOCHEMICAL substrates, OLIGOSACCHARIDES, CARRAGEENANS
Abstract

The marine Bacteroidota Zobellia galactanivorans has a polysaccharide utilization locus dedicated to the catabolism of the red algal cell wall galactan carrageenan and its unique and industrially important α‐3,6‐anhydro‐D‐galactose (ADG) monosaccharide. Here we present the first analysis of the specific molecular interactions that the exo‐(α‐1,3)‐3,6‐anhydro‐D‐galactosidase ZgGH129 uses to cope with the strict steric restrictions imposed by its bicyclic ADG substrate — which is ring flipped relative to D‐galactose. Crystallographic snapshots of key catalytic states obtained with the natural substrate and novel chemical tools designed to mimic species along the reaction coordinate, together with quantum mechanics/molecular mechanics (QM/MM) metadynamics methods and kinetic studies, demonstrate a retaining mechanism where the second step is rate limiting. The conformational landscape of the constrained 3,6‐anhydro‐D‐galactopyranose ring proceeds through enzyme glycosylation B1,4→[E4]≠→E4/1C4 and deglycosylation E4/1C4→[E4]≠→B1,4 itineraries limited to the Southern Hemisphere of the Cremer–Pople sphere. These results demonstrate the conformational changes throughout catalysis in a non‐standard, sterically restrained, bicyclic monosaccharide, and provide a molecular framework for mechanism‐based inhibitor design for anhydro‐type carbohydrate‐processing enzymes and for future applications involving carrageenan degradation. In addition, our study provides a rare example of distinct niche‐based conformational itineraries within the same carbohydrate‐active enzyme family. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

16. Conformational and Electronic Variations in 1,2‐ and 1,6‐Cyclophellitols and Their Impact on Retaining α‐Glucosidase Inhibition

Author

Ofman, Tim P., primary, Heming, Jurriaan J. A., additional, Nin-Hill, Alba, additional, Küllmer, Florian, additional, Moran, Elisha, additional, Bennett, Megan, additional, Steneker, Roy, additional, Klein, Anne-Mei, additional, Ruijgrok, Gijs, additional, Kok, Ken, additional, Armstrong, Zach W. B., additional, Aerts, Johannes M. F. G., additional, van der Marel, Gijsbert A., additional, Rovira, Carme, additional, Davies, Gideon J., additional, Artola, Marta, additional, Codée, Jeroen D. C., additional, and Overkleeft, Hermen S., additional

Published
2024
Full Text
View/download PDF

17. Light-Activated Agonist-Potentiator of GABAAReceptors for Reversible Neuroinhibition in Wildtype Mice

Author

Maleeva, Galyna, Nin-Hill, Alba, Wirth, Ulrike, Rustler, Karin, Ranucci, Matteo, Opar, Ekin, Rovira, Carme, Bregestovski, Piotr, Zeilhofer, Hanns Ulrich, König, Burkhard, Alfonso-Prieto, Mercedes, and Gorostiza, Pau

Abstract

Gamma aminobutyric acid type A receptors (GABAARs) play a key role in the mammalian central nervous system (CNS) as drivers of neuroinhibitory circuits, which are commonly targeted for therapeutic purposes with potentiator drugs. However, due to their widespread expression and strong inhibitory action, systemic pharmaceutical potentiation of GABAARs inevitably causes adverse effects regardless of the drug selectivity. Therefore, therapeutic guidelines must often limit or exclude clinically available GABAAR potentiators, despite their high efficacy, good biodistribution, and favorable molecular properties. One solution to this problem is to use drugs with light-dependent activity (photopharmacology) in combination with on-demand, localized illumination. However, a suitable light-activated potentiator of GABAARs has been elusive so far for use in wildtype mammals. We have met this need by developing azocarnil, a diffusible GABAergic agonist-potentiator based on the anxiolytic drug abecarnil that is inactive in the dark and activated by visible violet light. Azocarnil can be rapidly deactivated with green light and by thermal relaxation in the dark. We demonstrate that it selectively inhibits neuronal currents in hippocampal neurons in vitroand in the dorsal horns of the spinal cord of mice, decreasing the mechanical sensitivity as a function of illumination without displaying systemic adverse effects. Azocarnil expands the in vivophotopharmacological toolkit with a novel chemical scaffold and achieves a milestone toward future phototherapeutic applications to safely treat muscle spasms, pain, anxiety, sleep disorders, and epilepsy.

Published
2024
Full Text
View/download PDF

19. β-l-Arabinofurano-cyclitol Aziridines Are Covalent Broad-Spectrum Inhibitors and Activity-Based Probes for Retaining β-l-Arabinofuranosidases

Author

Borlandelli, Valentina, primary, Offen, Wendy, additional, Moroz, Olga, additional, Nin-Hill, Alba, additional, McGregor, Nicholas, additional, Binkhorst, Lars, additional, Ishiwata, Akihiro, additional, Armstrong, Zachary, additional, Artola, Marta, additional, Rovira, Carme, additional, Davies, Gideon J., additional, and Overkleeft, Herman S., additional

Published
2023
Full Text
View/download PDF

33. Discovery of processive catalysis by an exo-hydrolase with a pocket-shaped active site

Author

Streltsov, Victor A., Luang, Sukanya, Peisley, Alys, Varghese, Joseph N., Ketudat Cairns, James R., Fort, Sebastien, Hijnen, Marcel, Tvaroška, Igor, Ardá, Ana, Jiménez-Barbero, Jesús, Alfonso-Prieto, Mercedes, Rovira, Carme, Mendoza, Fernanda, Tiessler-Sala, Laura, Sánchez-Aparicio, José-Emilio, Rodríguez-Guerra, Jaime, Lluch, José M., Maréchal, Jean-Didier, Masgrau, Laura, and Hrmova, Maria

Published
2019
Full Text
View/download PDF

39. Phosphorylation disrupts long-distance electron transport in cytochrome c

Author

Gomila, Alexandre, primary, Pérez-Mejías, Gonzalo, additional, Hill, Alba Nin, additional, Guerra, Alejandra, additional, Casas-Ferrer, Laura, additional, Ortiz-Tescari, Sthefany, additional, Díaz-Quintana, Antonio, additional, Samitier, Josep, additional, Rovira, Carme, additional, Rosa, Miguel A. De la, additional, Díaz-Moreno, Irene, additional, Gorostiza, Pau, additional, Giannotti, Marina, additional, and Lagunas, Anna, additional

Published
2022
Full Text
View/download PDF

43. Phosphorylation disrupts long-distance electron transport in cytochrome c

Author

Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular, European Union (UE), Ministerio de Ciencia e Innovación (MICIN). España, Generalitat de Catalunya, Junta de Andalucía, Gomila, Alexandre M.J., Pérez Mejías, Gonzalo, Nin-Hill, Alba, Guerra Castellano, Alejandra, Casas Ferrer, Laura, Ortiz Tescari, Sthefany, Díaz Quintana, Antonio Jesús, Samitier, Josep, Rovira, Carme, Rosa Acosta, Miguel Ángel de la, Díaz Moreno, Irene, Gorostiza, Pau, Giannotti, Marina I., Lagunas, Anna, Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular, European Union (UE), Ministerio de Ciencia e Innovación (MICIN). España, Generalitat de Catalunya, Junta de Andalucía, Gomila, Alexandre M.J., Pérez Mejías, Gonzalo, Nin-Hill, Alba, Guerra Castellano, Alejandra, Casas Ferrer, Laura, Ortiz Tescari, Sthefany, Díaz Quintana, Antonio Jesús, Samitier, Josep, Rovira, Carme, Rosa Acosta, Miguel Ángel de la, Díaz Moreno, Irene, Gorostiza, Pau, Giannotti, Marina I., and Lagunas, Anna

Abstract

t has been recently shown that electron transfer between mitochondrial cytochrome c and the cytochrome c1 subunit of the cytochrome bc1 can proceed at long-distance through the aqueous solution. Cytochrome c is thought to adjust its activity by changing the affinity for its partners via Tyr48 phosphorylation, but it is unknown how it impacts the nanoscopic environment, interaction forces, and long-range electron transfer. Here, we constrain the orientation and separation between cytochrome c1 and cytochrome c or the phosphomimetic Y48pCMF cytochrome c, and deploy an array of single-molecule, bulk, and computational methods to investigate the molecular mechanism of electron transfer regulation by cytochrome c phosphorylation. We demonstrate that phosphorylation impairs long-range electron transfer, shortens the long-distance charge conduit between the partners, strengthens their interaction, and departs it from equilibrium. These results unveil a nanoscopic view of the interaction between redox protein partners in electron transport chains and its mechanisms of regulation.

Published
2022

44. Computer Simulation to Rationalize 'Rational' Engineering of Glycoside Hydrolases and Glycosyltransferases

Author

Coines, Joan, Cuxart, Irene, Teze, David, Rovira, Carme, Coines, Joan, Cuxart, Irene, Teze, David, and Rovira, Carme

Abstract

Glycoside hydrolases and glycosyltransferases are the main classes of enzymes that synthesize and degrade carbohydrates, molecules essential to life that are a challenge for classical chemistry. As such, considerable efforts have been made to engineer these enzymes and make them pliable to human needs, ranging from directed evolution to rational design, including mechanism engineering. Such endeavors fall short and are unreported in numerous cases, while even success is a necessary but not sufficient proof that the chemical rationale behind the design is correct. Here we review some of the recent work in CAZyme mechanism engineering, showing that computational simulations are instrumental to rationalize experimental data, providing mechanistic insight into how native and engineered CAZymes catalyze chemical reactions. We illustrate this with two recent studies in which (i) a glycoside hydrolase is converted into a glycoside phosphorylase and (ii) substrate specificity of a glycosyltransferase is engineered toward forming O-, N-, or S-glycosidic bonds.

Published
2022

48. Enzymatische C4‐Epimerisierung von UDP‐Glucuronsäure: präzise gesteuerte Rotation eines transienten 4‐Ketointermediats für eine invertierende Reaktion ohne Decarboxylierung.

Author

Borg, Annika J. E., Esquivias, Oriol, Coines, Joan, Rovira, Carme, and Nidetzky, Bernd

Subjects
ROTATIONAL motion
Abstract

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2023
Full Text
View/download PDF

49. Enzymatic C4‐Epimerization of UDP‐Glucuronic Acid: Precisely Steered Rotation of a Transient 4‐Keto Intermediate for an Inverted Reaction without Decarboxylation.

Author

Borg, Annika J. E., Esquivias, Oriol, Coines, Joan, Rovira, Carme, and Nidetzky, Bernd

Subjects
DECARBOXYLATION, ROTATIONAL motion, SYNTHASES, ACIDS, DECARBOXYLASES, SOCIAL interaction
Abstract

UDP‐glucuronic acid (UDP‐GlcA) 4‐epimerase illustrates an important problem regarding enzyme catalysis: balancing conformational flexibility with precise positioning. The enzyme coordinates the C4‐oxidation of the substrate by NAD+ and rotation of a decarboxylation‐prone β‐keto acid intermediate in the active site, enabling stereoinverting reduction of the keto group by NADH. We reveal the elusive rotational landscape of the 4‐keto intermediate. Distortion of the sugar ring into boat conformations induces torsional mobility in the enzyme's binding pocket. The rotational endpoints show that the 4‐keto sugar has an undistorted 4C1 chair conformation. The equatorially placed carboxylate group disfavors decarboxylation of the 4‐keto sugar. Epimerase variants lead to decarboxylation upon removal of the binding interactions with the carboxylate group in the opposite rotational isomer of the substrate. Substitutions R185A/D convert the epimerase into UDP‐xylose synthases that decarboxylate UDP‐GlcA in stereospecific, configuration‐retaining reactions. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results