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Galactitol-1-phosphate 5-dehydrogenase (GPDH) is a polyol dehydrogenase that catalyses the Zn2+ and NAD+-dependent stereoselective dehydrogenation of L-galactitol-1-phosphate to D-tagatose-6-phosphate. J.M. Mancheño (Dept. of Crystallography) in collaboration with Gert W. Kohring, Federico Gago and Rosario Muñoz, have reported three crystal structures of GPDH from Escherichia coli: the open state with Zn2+ in the catalytic site and also those of the closed state in complex with the polyols Tris and glycerol, respectively, but with no cofactor bound, which contrast with the behaviour of the prototypical mammalian liver alcohol dehydrogenase. Unexpectedly, a large internal cavity was found at the main contacting interface between GPDH subunits (GPDH is a dimer) that probably facilitates their relative movement. The binding mode of the substrate analogue glycerol reveals, for the first time in the polyol dehydrogenases, a penta-coordinated zinc ion in complex with a polyol and also a strong hydrogen bond with the conserved Glu144, an interaction originally proposed more than thirty years ago that supports a catalytic role for this acidic residue.

Rocío Benavente, María Esteban-Torres, Gert-Wieland Kohring, Álvaro Cortés-Cabrera, Pedro A. Sánchez-Murcia, Federico Gago, Iván Acebrón, Blanca De Las Rivas, Rosario Muñoz, José M. Mancheño. “Enantioselective oxidation of galactitol-1-phosphate by galactitol-1-phosphate 5-dehydrogenase from Escherichia coli”. Acta Crystallographica (2015) D71, 1540-1554. 
(doi: 10.1107/S1399004715009281)

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Amyotrophic Lateral Sclerosis (ALS) is a mortal neuromuscular disease that affects 2800 persons in Spain, with two new cases being diagnosed each day. Abnormal aggregates of the protein “TDP-43” (transactive response DNA binding protein 43 kDa) are found in >95% of dying motor neurons, and have been linked to other neurodegenerative disease, including Alzheimer’s disease and Frontotemporal Lobar Degeneration. Aggregation of TDP-43 was traced to a small, Asn- and Gln-rich region of the protein spanning residues 341-357, but the conformation of this segment and how it oligomerizes into harmful aggregates was unknown. Here, on the basis of multiple biochemical assays and biophysical experiments, IQFR investigators in collaboration with scientists from Columbia University (New York), the Cajal Institute (CSIC), IMDEA Nanoscience (CAM), and the International Centre for Genetic Engineering and Biotechnology (Trieste, IT) show that this segment’s beta hairpin motifs assemble into an amyloid-like structure with an unusual fibril morphology. Using computational methods, they have advanced an amyloid-like structural model for the aggregate in which TDP-43 (341-357) beta hairpins dock in a novel, parallel topology. This structural model will likely aid our understanding of TDP-43’s role in neurodegenerative diseases and may help guide the search for treatments.

M. Mompeán, R. Hervás, Y. Xu, T.H. Tran, C. Guarnaccia, E. Buratti, F. Baralle, L. Tong, M. Carrión-Vázquez, A.E. McDermott, D.V. Laurents 
J. Phys. Chem. Letters, June 2015, doi: 10.1021/acs.jpclett.5b00918

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Autolysin LytA is a protein involved in the virulence of pneumococcus, a pathogenic microorganism in humans. Its C-terminal domain (CLytA) consists of six choline-binding repeats (CBR), arranged in the β-solenoid structure characteristic of choline-binding modules. In the NMR group of the Institute of Physical-Chemistry ‘Rocasolano’ (CSIC) we have structurally characterised a 14-residue peptide encompassing the sequence of the core β-hairpin from the third CBR repeat of CLytA. It has been found that this peptide conserves its native β-hairpin fold in aqueous solution, but forms a stable, amphipathic α-helix (i.e. with two faces, one hydrophobic and the other polar) in detergent micelles (with a hydrophilic surface and a hydrophobic core). These β-hairpin and α-helix structures differ greatly in the distribution of polar hydrophobic side chains. As far as we know, this "chameleonic" behaviour of a micelle-induced structural transition between two ordered peptide structures has not been reported before, and shows the dramatic effect of hydrophobic-hydrophilic interactions. These results could not only be of relevance in the field of peptide design and biosensors, but may also help to understand the molecular basis for the peculiar mechanism of LytA translocation from the cytoplasm to the bacterial surface.
Reference:

Hector Zamora-Carreras, Beatriz Maestro, Erik Strandberg, Anne S. Ulrich, Jesús M. Sanz, y M. Angeles Jiménez. “Micelle-triggered β-hairpin to α-helix transition in a 14-residue peptide derived from the pneumococcal choline-binding protein LytA”. Chemistry-Eur J. 21, 8076-8089 (2015). doi:10.1002/chem.201500447
Enlace a artículos destacados en mayo 2015 por la SBE (http://biofisica.info/zamora-carreras-jimenez-chemistry-21-8076/) 

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Plant cell walls are highly complex structures of interlocking polysaccharides that are recalcitrant to biological degradation. Within the complex molecular machinery involved in its deconstruction, one of the greatest challenges is to decipher the mechanism that display enzymes with multiple copies of ancillary non-catalytic domains. Most of these domains are Carbohydrate Binding Modules (CBMs). Homogeneous multimodularity has been related to multivalency and avidity effects, while heterogeneous pattern is supposed to provide distinct substrate-binding specificities. However, recent work suggests that this panorama may be more complex. Researchers at IQFR have performed structural and functional studies on a large xylanase (Xyn10c) showing a distinctive modular structure that contains an N-terminal tandem of two CBM22s and a duplicated CMB9 at its C-terminus. We have discovered novel features that attribute a different functionality to each CBM22 module and suggest a deliver strategy of Xyn10C mediated by its CBM22 tandem. Our work will contribute to unravel the mechanisms ruling modularity, which is essential to understand the biomass recycling and to produce efficient biocatalysts. This will result in more environmentally sustainable industries.

The Journal of Biological Chemistry (2015)
First published in May 22
(doi:10.1074/jbc.M115.659300)