Selenocysteine (Sec), the 21^st amino acid specified by the genetic code, is a rare selenium-containing residue found in the catalytic site of selenoprotein oxidoreductases. Sec is analogous to the common cysteine (Cys) amino acid but its selenium atom offers physicalchemical properties not provided by the corresponding sulfur atom in Cys. Catalytic sites with Sec in selenoproteins of vertebrates are under strong purifying selection but one enzyme, Glutathione Peroxidase 6 (GPX6), independently exchanged Sec for Cys less than one hundred million years ago in several mammalian lineages. We reconstructed and assayed these ancient enzymes before and after Sec was lost and up to today, and found them to have lost their classic ability to reduce hydroperoxides using glutathione (GSH). This loss of function, however, was accompanied by bursts of amino acid changes in the catalytic domain, with protein sites concertedly changing under positive selection across distant lineages abandoning Sec in GPX6. This demonstrates that when sulfur in Cys impairs catalysis a narrow evolutionary path is followed, with epistasis and pleiotropy leading to convergent evolution and triggering enzymatic properties likely beyond those in classic GPXs. These findings are an unusual example of adaptive convergence towards unexplored oxidoreductase functions during mammalian evolution.

• Preprint: Ancient loss of catalytic selenocysteine spurred convergent adaptation in a mammalian oxidoreductase. Jasmin Rees, Gaurab Sarangi, Qing Cheng, Martin Floor, Aida M Andrés, Baldomero Oliva Miguel, Jordi Villà-Freixa, Elias SJ Arnér, Sergi Castellano BioRxiv doi: https://doi.org/10.1101/2023.01.03.522577
• Published article: Ancient Loss of Catalytic Selenocysteine Spurred Convergent Adaptation in a Mammalian Oxidoreductase. Jasmin Rees, Gaurab Sarangi, Qing Cheng, Martin Floor, Aida M Andrés, Baldomero Oliva Miguel, Jordi Villà-Freixa, Elias S J Arnér, Sergi Castellano Genome Biology and Evolution, Volume 16, Issue 3, March 2024, evae041, https://doi.org/10.1093/gbe/evae041

Hereditary hemochromatosis (HH) is an iron metabolism disease clinically characterized by excessive iron deposition in parenchymal organs such as liver, heart, pancreas, and joints. It is caused by mutations in at least five different genes. HFE hemochromatosis is the most common type of hemochromatosis, while non-HFE related hemochromatosis are rare cases. Here, we describe six new patients of non-HFE related HH from five different families. Two families (Family 1 and 2) have novel nonsense mutations in the HFE2 gene have novel nonsense mutations (p.Arg63Ter and Asp36ThrfsTer96). In this new collaborative article led by Mayka Sánchez from the Department of Basic Sciences at UIC Barcelona, our lab gave the structural context for the effect of the identified mutations in TFR2 interactions.

Comparative modeling of the TFR2 dimer complexed with TF. (A) TFR2 chains are shown in cyan and pink, while TF chains are shown in green and orange. Dimeric interactions between TFR2 chains, close to Asp680 position (red circle at the α-15 helix, pink chain), are made between residues in the α-18 helix of one TFR2 chain (pink chain) and the loop located between the β-6 and β-7 strands of the other (cyan chain). (B) Sequence alignment of the TFR1 and TFR2 proteins near the TFR2 680 position (green arrow). Numbering is according to the TFR1 sequence, and the secondary structure depiction is based on the TFR1 structure (PDB ID 1CX8). The alignment coloring was produced by the ESPript 3.0 web server [40], where position with red background means absolute sequence conservation. (C–E) Structural context of positions TFR1-Asp648 (C, purple), TFR2-Asp680 (D, pink), and TFR2-Asp680Tyr (E, magenta). Residue names of TFR1/2 appear in white, while residues in TF are in black. Significant interactions are shown with dashed lines.

Hernández, G.; Ferrer-Cortès, X.; Venturi, V.; Musri, M.; Pilquil, M.F.; Torres, P.M.M.; Rodríguez, I.H.; Mínguez, M.À.R.; Kelleher, N.J.; Pelucchi, S.; Piperno, A.; Alberca, E.P.; Ricós, G.G.; Giró, E.C.; Pérez-Montero, S.; Tornador, C.; Villà-Freixa, J.; Sánchez, M. New Mutations in HFE2 and TFR2 Genes Causing Non HFE-Related Hereditary Hemochromatosis. Genes 2021, 12, 1980. https://doi.org/10.3390/genes12121980

Martin Floor presented a poster at the IV workshop on Bioinformatics and Genomics, jointly organized by the Catalan Biological Society and Bioinformatics Barcelona. The poster shows preliminary results on the effect of the AZ28 catalytic antibody on the Oxy-Cope rearrangement reaction by using EVB calculations.

The computational biochemistry and biophysics laboratory was created at the UPF in 2003 and remained there until May 2012, when I moved to the UVic-UCC. After a couple of years of strong managerial work that diverted the main research efforts of the lab, it is now rebuilding with evolved lines of research within the framework of the Bioinformatics and Medical Statistics Research Group. To make the story short, the CBBL devotes more and more to collaborative work with experimentalists, and a number of projects dealing with computational structural biology are being undertaken by the lab members. See the publications page for more details.

On the other hand, the interest of the lab to develop its own tools when needed is more than alive, and the combination between methodological development and applied research is the driving force of our members.

A la reunió plenària del Patronat de la Fundació Universitària Balmes, celebrada dijous passat a l’Atlàntida, entre moltes altres qüestions, es va aprovar el nou equip de Rectorat amb la incorporació del Dr. Jordi Villà com a nou vicerector de Recerca i també de de Personal Docent i Investigador.
Més informació: VilaWeb

Diari ARA, 08/06/2014

La recerca bàsica, malgrat el sotrac de la crisi, ha experimentat al nostre país un avenç sense precedents en els darrers 15 anys, i ens ha situat com a pol d’atracció de talent reconegut internacionalment. En paral·lel, el teixit industrial català surt fortament tocat d’aquesta crisi, però per la seva capacitat de resistència i regeneració comença a donar signes de recuperació. Sortosament, són cada cop més els exemples de la integració de l’R+D+I al disseny i execució de processos productius, però encara som lluny d’exemples exitosos d’altres regions. Per obtenir les sinergies necessàries en aquest procés de reflotament, és imprescindible, doncs, un major diàleg entre els mons de la universitat i l’empresa.

És en aquest context que la Generalitat de Catalunya va llançar el 2012 una proposta engrescadora per incorporar talent a les empreses allà on han de reforçar el seu creixement. El Govern va identificar que la transferència de coneixement havia de donar pas a la concurrència d’interessos entre ambdós mons, i és en els recursos humans on aquesta col·laboració universitat-empresa s’accentua.

D’aquest esforç sorgeix el programa de doctorats industrials, en el qual la UVic-UCC té una participació molt activa. De la bona entesa en la triple hèlix empresa-administració-universitat n’estan sorgint propostes que impulsen nova riquesa basada en el coneixement i la seva aplicació que, sens dubte, ens ajudaran a superar aquests moments de depressió econòmica i anímica.