Research

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Magnetite is a magnetic material known since more than two thousand years ago. It presents a phase transition known as the Verwey transition (at ~ 120K), in which the crystal structure changes from cubic to monoclinic, and at the same time the conductivity is reduced by two orders of magnitude. This transition strongly promoted research on metal-insulator transitions. For the first time, a team of researchers from the IQFR, Berkeley National Laboratory and the Vienna Technical University have observed this transition with surface-sensitive microscopies for the (100) orientation of magnetite. It has been found that the surface "rumbles" forming a roof-like surface at a micrometer scale, whereas the actual surface reconstruction has the same structure through the transition. This indicates that although the surface reconstruction is conceptually similar to the bulk structure below the transition, they are two distinct phenomena.

J. de la Figuera, Z. Novotny, M. Setvin, T. Liu, Z. Mao, G. Chen, A. T. N'Diaye, M. Schmid, U. Diebold, A. K. Schmid, G. S. Parkinson, "Real Space Imaging of the Verwey Transition at the (100) Surface of Magnetite", Phys. Rev. B 88 (2013) 161410(R), DOI:10.1103/PhysRevB.88.161410, arxiv 1310.1373

The figure shows at the top, low-energy electron microscope images (8.6 um wide) above (left) and below (right) the Verwey transition. In the middle, scanning tunneling microscopy images with atomic resolution are shown also above and below the transition. At the bottom, a profile showns the "roof" surface below the transition.

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The expression of penicillin binding protein 2a (PBP2a) is the basis for the broad clinical resistance to the β-lactam antibiotics by methicillin-resistant Staphylococcus aureus (MRSA). The highmolecular mass penicillin binding proteins of bacteria catalyze in separate domains the transglycosylase and transpeptidase activities required for the biosynthesis of the peptidoglycan polymer that comprises the bacterial cell wall. In bacteria susceptible to β-lactam antibiotics, the transpeptidase activity of their penicillin binding proteins (PBPs) is lost as a result of irreversible acylation of an active site serine by the β-lactam antibiotics. In contrast, the PBP2a of MRSA is resistant to β-lactamacylation and successfully catalyzes the DD-transpeptidation reaction necessary to complete the cell wall. The inability to contain MRSA infection with β-lactam antibiotics is a continuing public health concern. We report herein the identification of an allosteric binding domain—a remarkable 60 Å distant from the DD-transpeptidase active site—discovered by crystallographic analysis of a soluble construct of PBP2a. When this allosteric site is occupied, a multiresidue conformational change culminates in the opening of the active site to permit substrate entry. This same crystallographic analysis also reveals the identity of three allosteric ligands: muramic acid (a saccharide component of the peptidoglycan), the cell Wall peptidoglycan, and ceftaroline, a recently approved anti-MRSA β-lactam antibiotic. The ability of an anti-MRSA β-lactam antibiotic to stimulate allosteric opening of the active site, thus predisposing PBP2a to inactivation by a second β-lactam molecule, opens an unprecedented realm for β-lactam antibiotic structure-based design.

Reference:

Lisandro H. Oteroa, Alzoray Rojas-Altuvea, Leticia I. Llarrull, Cesar Carrasco-López, Malika Kumarasiri, Elena Lastochkin, Jennifer Fishovitz, Matthew Dawley, Dusan Hesek, Mijoon Lee, Jarrod W. Johnson, Jed F. Fisher, Mayland Chang, Shahriar Mobashery, Juan A. Hermoso. How allosteric control of Staphylococcus aureus penicillin binding protein 2a enables methicillin resistance and physiological function. PNAS. DOI: 10.1073/pnas.1300118110

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Modified nucleic acids are very interesting molecules because of their application in Biomedicine, as therapeutic agents, and in Nanoscience, as potential components of nano-devices. Of particular relevance is the substitution of a hydrogen atom at the 2’ position of the DNA deoxyribose by fluorine. Fluorine is the most electronegative element and alters the electronic distribution in its surroundings, provoking interactions that are not present, or are much weaker, in natural nucleic acids.

In two recent papers researchers of the IQFR, in collaboration with colleagues of McGill University in Canada and in the IRB in Barcelona, have described these effects at structural level and analysed their physico-chemical basis in double helical and guanine quadruplex structures.

Reference:

N. Martín-Pintado, M. Yahyaee-Anzahaee, G. F. Deleavey, G. Portella, M. Orozco, M.J. Damha, and C. González.Dramatic effect of furanose C2´-substitution on structure and stability: Directing the folding of the human telomeric quadruplex with a single fluorine atom.J. Am. Chem. Soc., 135, 5344-5347, 2013.doi: 10.1021/ja401954t

N. Martín-Pintado, G. F. Deleavey, G. Portella, R. Campos-Olivas, M. Orozco, M.J. Damha, and C. González.Backbone FC-H...O hydrogen bonds in 2´F-substituted nucleic acids.Angewandte Chemie Int Ed, en prensa, 2013.doi:10.1002/anie.201305710

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Scientists from the Department of Biophysical Chemistry discovered novel water-soluble oxocines and azocines that produce blue fluorescence with 100% quantum yield. These molecules are the main product of a new fluorogenic reaction that converts non-emitting biocompounds as L-DOPA, dopamine, hydroxytyrosol, etc. into useful photostable fluorophores. The new molecular structures contain the rare four-ring chromophore which originated the first written account of fluorescence emission in 1565 (Acuña et al. Org. Lett. 2009, 11, 3020). At that time, the medical doctor N. Monardes from Sevilla reported the unusual blue “color” (fluorescence) of the infusion of a medicinal wood widely used in preHispanic Aztec culture.

Reference:

Synthesis and photophysics of novel biocompatible fluorescent oxocines and azocines in aqueous solution.

A.Ulises Acuña, Mónica Älvarez-Pérez, Marta Liras, Pedro B. Coto and Francisco Amat-Guerri.

Phys. Chem. Chem. Phys. Sept. 2013 (DOI: 10:1039/c3cp52228h)

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nap2p Nab2p is an essential protein involved in mRNP (messenger ribonucleoprotein particles) formation and export in Saccharomyces cerevisiae. Its specific poly(A) RNA recognition ability resides on a region containing 7 CCCH-type zinc finger domains, of which, the last three zinc finger structure was previously known. In our group, we have solved the NMR structure of the first 4 zinc fingers that show novel elements in their fold. The first two zinc fingers (Zf1 and Zf2) form a compact tandem stabilized by a new -helix contacting both. Zf3 and Zf4 form a second tandem in which the metallic centres associate in a singular symmetric way with mutual recognition of the Zn²⁺ coordinating histidines. NMR, fluorescence anisotropy and mutagenesis studies identify the -helix in the first tandem and the exposed surface of Zf3 as the RNA binding interface. Our results allow us to propose a recognition model where Nab2p Zf1-4 cooperates with Nab2p Zf5-7 to reconstitute the poly(A) binding profile of the full-length protein.