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A complex link exists between cell-wall recycling/repair and the manifestation of resistance to β-lactam antibiotics in many Enterobacteriaceae and Pseudomonas aeruginosa. This process is mediated by specific cell-wall-derived muropeptide products. These muropeptides are internalized into the cytoplasm and bind to the transcriptional regulator AmpR, which controls the cytoplasmic events that lead to expression of β-lactamase, an antibiotic-resistance determinant. By a combination of X-ray crystallography, mass spectrometry and molecular dynamics techniques we have characterized the effector-binding domain (EBD) of AmpR. Our results provide insights on the muropeptides triggering antibiotics resistance and revises the dogma in the field.
This is part of a collaborative effort between the IQFR and the Univ. of Notre Dame (Indiana, USA).

Dik, D.A.; Domínguez-Gil, T.; Lee, M.; Hesek, D.; Byun, B.; Fishovitz, J.; Boggess, B.; Hellman, L.M.; Fisher, J. F.; Hermoso, J.A.; Mobashery, S. “Muropeptide Binding and the X-Ray Structure of the Effector Domain of the Transcriptional Regulator AmpR of Pseudomonas aeruginosa”. J. Am. Chem. Soc. (2017).
doi:10.1021/jacs.6b12819

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Category: Research

We study thermochemical [1] and electronic properties [2] of halogen-containing species with relevance to several atmospherical processes (e.g. catalytic ozone destruction and air quality).
On the one hand, we found that Gn (Gaussian-n, n = 3,4) ab initio computations are accurate theoretical methods to provide reliable heat of formation and carbon-halogen bond-energy values of a wide variety of chlorinated and brominated organic species [1]. These data will be implemented in climate models in order to evaluate the atmospheric-impact of these compounds.

On the other hand, we have shown that the CASPT2 methodology ("Complete Active Self Consistent Field Perturbation Theory”) is also an excellent method for providing reliable values of absorption optical parameters (within the UV-Vis range) of representative species such as IBr and HgBr2 which have particular connotation in photochemical atmospheric processes [2].

[1] J.Z. Dávalos, R. Notario, C.A. Cuevas, J.M. Oliva, A. Saiz-Lopez: “Thermochemistry of halogen-containing organic compounds with influence on atmospheric chemistry”. Comp. Theor. Chem. 1099 (2017) 36-44. DOI:10.1016/j.comptc.2016.11.009
[2] S.P. Sitkiewicz, J.M. Oliva, J.Z. Dávalos, R. Notario, A. Saiz-Lopez, D.R. Alcoba, O.B. Oña, D. Roca-Sanjuán; “Ab initio quantum-chemical computations of the electronic states in HgBr2 and IBr: Molecules of interest on the Earth's atmosphere”. J. Chem. Phys. 145 (2016) 244304, 1-14. DOI:10.1063/1.4971856

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Magnetite is the material used to track the history of the Earth magnetic field. Thus its magnetism, and especially its changes with temperature, have attracted a long-standing interest. Magnetite undergoes several phase transitions, some purely magnetic, like the spin-reorientation transition (typically at 130-140K) where the magnetization changes direction, and others, like the Verwey transition, a metal-insulator transition due to a change in the crystal structure, from cubic to monoclinic. We have recently employed novel microscopy techniques to observe the changes of magnetic domains due to these transitions: one, spin-polarized low-energy electron microscopy (SPLEEM), of which there are four instruments in the world, in collaboration with Andreas K. Schmid and coworkers from the Berkeley National Laboratory, and the other, spin-resolved photoemission electron microscopy (spin-PEEM), of which there is currently only one instrument, at the Max Planck Insitute for Microstructure Physics (Halle), in collaboration with Christian Tusche. Upper left-hand figure: SPLEEM image of the magnetic domains below the Verwey temperature, color-coded for the orientation of the magnetization as shown in the circle below (1). Right-hand figure: spin-PEEM image (2) of the magnetization above (upper image) and below (lower image) the Verwey temperature. These techniques allowed us to obtain images with nm resolution of the magnetic domains below and above the transition temperature.

(1) Laura Martín-García, Arantzazu Mascaraque, Beatriz M. Pabón, Roland Bliem, Gareth S. Parkinson, Gong Chen (陈宫), Andreas K. Schmid, and Juan de la Figuera, "Spin reorientation transition on magnetite (001)", Phys. Rev. B 93 (2016) 134419, DOI:10.1103/PhysRevB.93.134419

(2) J. de la Figuera and C. Tusche, "The Verwey transition observed by spin-resolved photoemission electron microscopy", App. Surf. Sci. (2016), DOI:10.1016/j.apsusc.2016.05.140

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The discovery of stable amyloids composed solely of polar residues surprised scholars who believed that protein conformational stability is chiefly due to the hydrophobic effect. These amyloids, rich in Asn and Gln residues, form extensive hydrogen bonding networks. When aligned, hydrogen bond networks are strengthened due to cooperative effects arising from hyperpolarization. In this work, Density Functional Theory and Natural Bonding Orbital analysis were applied to study a series of polar and hydrophobic peptides in amyloid-like oligomers of different sizes and revealed that hydrogen bond networks formed by Asn and Gln side chains experience a distinct class of cooperativity that strengthens them significantly relative to main chain hydrogen bond networks. These computational results were corroborated experimentally utilizing recognition by amyloid specific molecular probes, nuclear magnetic resonance spectroscopy and experimental electric conductivity measurements on Asn/Gln-rich and hydrophobic peptides. On the basis of these findings, approaches to selectively inhibit the formation of polar versus hydrophobic amyloids can now be devised.

The figure shows a schematic representation of the delocalized electron density (blue shading) in the H-bond networks formed by Asn side chains (left) and the peptide backbone (right).

Miguel Mompeán, Aurora Nogales, Tiberio A. Ezquerra & Douglas V. Laurents ( "Complex System Assembly Underlies a Two-Tiered Model of Highly Delocalized Electrons" J. Phys. Chem. Lett. (2016) 7(10): 1859-1864.
(doi:10.1021/acs.jpclett.6b00699)