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iqfr enThe Institute of Physical Chemistry "Rocasolano" (IQFR) is located at the seat of the former National Institute of Physics and Chemistry, that in the period 1932-1936 spearheaded Spanish science. These days, the research interests of the IQFR range from fundamental aspects of physical chemistry to nanoscience and atmospheric chemistry or the application of physical-chemical techniques to problems of biological interest. Our research priorities include a variety of subjects, such as structural biology, functional biophysics, chemical kinetics and reactivity, computational chemistry and physics, laser design and applications, or surface structure and chemistry, together with other topics connected to interdisciplinary research in the field materials science and nanotechnology and the molecular basis of biological processes.

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Dr. Antonio Chaves-Sanjuán awarded with the 2017 “José Tormo” Prize of the Spanish Society of Biochemistry and Molecular Biology

Tormo Prize 2017In collaboration with BRUKER Española S.A., the SEBBM has awarded Dr. Antonio Chaves-Sanjuán with the “José Tormo” Prize for his work published in PNAS in 2017 and performed at Dr MJ Sánchez-Barrena Lab from the Dept. of Crystallography and Structural Biology, Institute “Rocasolano”.

This prize gives recognition to the best piece of work performed by a young researcher in a Spanish laboratory, and published during 2016-2017 in any of the areas related to Structural Biology. Dr. Chaves-Sanjuán will give a conference entitled “Las fenotiazinas regulan la función sináptica interfiriendo en la formación del complejo NCS-1/Ric8a: Un nuevo enfoque para el síndrome X frágil” at the XL Congress of the SEBBM, that will be held in Barcelona (23rd-26th October 2017).

 

 

“Leonardo” fellowship from Fundación BBVA granted to Dr. María José Sánchez Barrena

mariajosesanchez bbvaDr. M.J. Sánchez-Barrena, contracted researcher at Institute “Rocasolano”, has been awarded with a very competitive “Leonardo” fellowship from the BBVA Foundation. She will be able to continue her research on synapse alterations (contact among neurons) that are present, among others, in pathologies such as Alzheimer´s, dementia or Huntington disease. Her research is aimed to design molecules that are able to restore these contacts, avoiding memory loss and improving cognitive ability in earlier stages of the disease.
ABC press release

 

 

Highlights

LpBglStatistics from structural genomics initiatives reveal that around 50-55% of the expressed, non-membrane proteins cannot be purified and therefore structurally characterized due to solubility problems, which emphasized protein solubility as one of the most serious concerns in structural biology projects. Lactobacillus plantarum CECT 748T produces an aggregation-prone glycosidase (LpBgl) that we crystallized previously. However, this result could not be reproduced due to protein instability and therefore further high-resolution structural analyses of LpBgl were impeded. The obtained crystals of LpBgl diffracted up to 2.48Å resolution and permitted to solve the structure of the enzyme. Analysis of the active site revealed a pocket for phosphate-binding with an uncommon architecture, where a phosphate molecule is tightly bound suggesting the recognition of 6-phosphoryl sugars. In agreement with this observation, we showed that LpBgl exhibited 6-phospho-β-glucosidase activity. Combination of structural and mass spectrometry results revealed the formation of dimethyl arsenic adducts on the solvent exposed cysteine residues Cys211 and Cys292. Remarkably, the double mutant Cys211Ser/Cys292Ser resulted stable in solution at high concentrations indicating that the marginal solubility of LpBgl can be ascribed specifically to these two cysteine residues. Notably, LpBgl could be prepared at high yield by proteolytic digestion of the fusion protein LSLt-LpBgl, which raises important questions about potential hysteretic processes upon its initial production as an enzyme fused to a solubility enhancer.

Acebrón I, Plaza-Vinuesa L, de Las Rivas B, Muñoz R, Cumella J, Sánchez-Sancho F, Mancheño JM. “Structural basis of the substrate specificity and instability in solution of a glycosidase from Lactobacillus plantarum”. Biochim Biophys Acta. 1865(10):1227-1236. (2017).
doi: 10.1016/j.bbapap.2017.07.007

 

LmPDTProcesses catalyzed by enzymes offer numerous advantages over chemical methods although in many occasions the stability of the biocatalysts becomes a serious concern. Traditionally, synthesis of nucleosides using poorly water-soluble purine bases, such as guanine, xanthine or hypoxanthine, requires alkaline pH and/or high temperatures in order to solubilize the substrate. In this work, we demonstrate that the 2´-deoxyribosyltransferase from Leishmania mexicana (LmPDT) exhibits an unusually high activity and stability under alkaline conditions (pH 8-10) across a broad range of temperatures (30-70 ºC) and ionic strengths (0-500 mM NaCl). Conversely, analysis of the crystal structure of LmPDT together with comparisons with hexameric, bacterial homologs revealed the importance of the relationships between the oligomeric state and the active site architecture within this family of enzymes. Moreover, molecular dynamics and docking approaches provided structural insights into the substrate-binding mode.

Biochemical characterization of LmPDT identifies the enzyme as a type I NDT (PDT), exhibiting excellent activity, with specific activity values 100- and 4000-fold higher than the ones reported for other PDTs. Interestingly, LmPDT remained stable during 36 hours at different pH values at 40 °C. In order to explore the potential of LmPDT as an industrial biocatalyst, enzymatic production of several natural and non-natural, therapeutic nucleosides, such as vidarabine (ara A), didanosine (ddI), ddG or 2´-fluoro-2´-deoxyguanosine, was carried out using poorly water soluble purines. Noteworthy, this is the first time that the enzymatic synthesis of 2´-fluoro-2´-deoxyguanosine, ara G and ara H by a 2´-deoxyribosyltransferase is reported.

Crespo N, Sánchez-Murcia PA, Gago F, Cejudo-Sanches J, Galmes MA, Fernández-Lucas J, Mancheño JM. “2'-Deoxyribosyltransferase from Leishmania mexicana, an efficient biocatalyst for one-pot, one-step synthesis of nucleosides from poorly soluble purine bases”. Appl Microbiol Biotechnol (2017).
doi: 10.1007/s00253-017-8450-y

 

photoregulationLiving organisms sense and respond to light, a crucial environmental factor, using photoreceptors, which rely on bound chromophores such as retinal, flavins, or linear tetrapyrroles for light sensing. The discovery of photoreceptors that sense light using 5'-deoxyadenosylcobalamin, a form of vitamin B12 that is best known as an enzyme cofactor, expanded the number of known photoreceptor families and unveiled a new biological role of this vitamin. The prototype of these B12-dependent photoreceptors, the transcriptional repressor CarH, is widespread in bacteria and mediates light-dependent gene regulation in a photoprotective cellular response. CarH activity as a transcription factor relies on the modulation of its oligomeric state by 5'-deoxyadenosylcobalamin and light. This article surveys current knowledge of this new family of B12-dependent photoreceptors, their discovery, distribution and mode of action, and the structural and photochemical basis of how they orchestrate signal transduction and control gene expression. The main focus of the review is largely based on results stemming from the collaborative work by members of IQFR and the Dpto. de Genética-Universidad de Murcia (Unidad Asociada al IQFR), and more recently with groups in MIT (USA), and the Univ. Manchester (UK) that have been published in, among others, PNAS, Nature Communications and Nature. This article is an invited review by Prof. Roger Kornberg (Nobel Prize in Chemistry, 2006) on behalf of the Editorial Committee of Annu Rev Biochem.

S. Padmanabhan, Marco Jost, Catherine L. Drennan, and Montserrat Elías-Arnanz. “A New Facet of Vitamin B12: Gene Regulation by Cobalamin-Based Photoreceptors”. Annu Rev Biochem 86, 485–514 (2017).
DOI: 10.1146/annurev-biochem-061516-044500

 

NagZThe N-acetylglucosaminidase NagZ of Pseudomonas aeruginosa catalyzes the first cytoplasmic step in recycling of muropeptides, cell-wall-derived natural products. This reaction regulates gene expression for the β-lactam resistance enzyme, β-lactamase. The structural and functional aspects of catalysis by NagZ were investigated by a total of seven X-ray structures, three computational models based on the X-ray structures, molecular-dynamics simulations and mutagenesis. The structural insights came from the unbound state and complexes of NagZ with the substrate, products and a mimetic of the transient oxocarbenium species. The catalytic mechanism involves a histidine as an acid/base catalyst, which is unique in glycosidases and is inhibited by zinc ion. This analysis provides a seamless continuum for the catalytic cycle, incorporating the large motions by loops that surround the active site. This is part of a collaborative effort between the IQFR and the Univ. of Notre Dame (Indiana, USA).

Acebrón, I.; Mahasenan, K.; De Benedetti, S.; Lee, M.; Artola-Recolons, C.; Hesek, D.; Wang, H.; Hermoso*, J.A.; Mobashery*, S. “Catalytic Cycle of the N-Acetylglucosaminidase NagZ from Pseudomonas aeruginosa”. J. Am. Chem. Soc. (2017).
DOI:10.1021/jacs.7b01626

 

LombaCoincident with the anniversary of the demise of our colleague Noé García Almarza, Soft Matter has published one of his last research studies that has also been highlighted in the Inside Front Cover of the aforementioned journal. In this work the self-assembly of spherical particles with three attractive sites distributed symmetrically along the particle equator was investigated under planar confinement. The study of this type of colloidal systems is interesting both from a practical point of view, for the design of new materials with properties 'a la carte', and from a fundamental one, as they often exhibit unusual physical behavior. Indeed, in this article, it is shown that, under certain conditions, these trivalent particles assemble into a rather exotic hybrid solid-gas phase formed by a honey-comb lattice and a gas of particles located at the lattice voids. The concentration of particles at the interstices of the honey-comb lattice varies continuously with pressure without undergoing a true thermodynamic transition, so that at low pressure all the voids are empty, whereas at high pressure all are occupied forming a triangular lattice. The Mechanical Statistics and Condensed Matter group dedicates this work to the memory of our dear friend Noé.

Eva G. Noya, Noé G. Almarza & Enrique Lomba. “Assembly of trivalent particles under confinement: from an exotic solid phase to a liquid phase at low temperature”. Soft Matter 13, 3221 (2017).
DOI:10.1039/C7SM00217C

 

 

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