I was at the 19th YSF and 44th FEBS conferences, in Krakow – Poland, during the last week (July 3rd to 11th) presenting my work about “Enhancing the catalytic power of Serine Hydroxymethyltransferase to produce commercially valuable compounds”. It was an excellent congress where I got some new ideas for the future. Thank you
Henrique S. Fernandes, Sérgio F. Sousa, and Nuno M.F.S.A. Cerqueira
Nature has tailored a wide range of metalloenzymes that play a vast array of functions in all living organisms and from which their survival and evolution depends on. These enzymes catalyze some of the most important biological processes in nature, such as photosynthesis, respiration, water oxidation, molecular oxygen reduction, and nitrogen fixation. They are also among the most proficient catalysts in terms of their activity, selectivity, and ability to operate at mild conditions of temperature, pH, and pressure. In the absence of these enzymes, these reactions would proceed very slowly, if at all, suggesting that these enzymes made the way for the emergence of life as we know today. In this review, the structure and catalytic mechanism of a selection of diverse metalloenzymes that are involved in the production of highly reactive and unstable species, such as hydroxide anions, hydrides, radical species, and superoxide molecules are analyzed. The formation of such reaction intermediates is very difficult to occur under biological conditions and only a rationalized selection of a particular metal ion, coordinated to a very specific group of ligands, and immersed in specific proteins allows these reactions to proceed. Interestingly, different metal coordination spheres can be used to produce the same reactive and unstable species, although through a different chemistry. A selection of hand-picked examples of different metalloenzymes illustrating this diversity is provided and the participation of different metal ions in similar reactions (but involving different mechanism) is discussed.
I would like to thank the Organising Committee of the VII AEICBAS Biomedical Congress (2019, March 17th) for the invitation to share my experience as a biochemist.
Is the 5,10methylenetetrahydrofolate cofactor synthesized through a non-enzymatic or enzymatic mechanism?
Fernandes, H. S., Sousa, S. F., and Cerqueira, N. M. F. S. A.
Last Saturday (November 17th), I was presenting some of the software that we have developed at BioSIM research group to improve the way some chemical concepts are taught to our students.
VMD extensions, such as VMD Magazine, ToolBar, Protein Wars, and VMD Store were presented during the “VII Encontro da Divisão de Ensino e Divulgação da Química” conference. During the presentation, the software features were presented and were showed how these extensions can be used to engage young students to learn chemistry in a more pleasant and clear manner.
Moreover, the BioSIM Augmented Reality technology was presented for the first time, and it allows an easy and costless way to see molecules using augmented reality. See the video below:
On September 28-29, I was presenting my recently published work at the UCIBIO Annual Meeting in Lisbon (FCT-NOVA).
The catalytic mechanism of Serine Hydroxymethyltransferase: a drug target against Malaria
Henrique S. Fernandes, M. J. Ramos, Sérgio F. Sousa, and N. M. F. S. A. Cerqueira
Henrique Silva Fernandes, Maria João Ramos, and Nuno M.F.S.A. Cerqueira
Published on 18th September 2018
Journal: ACS Catalysis
Serine Hydroxymethyltransferase (SHMT) is an important drug target to fight malaria – one of the most devastating infectious diseases that accounted in 2016 with 216 million new cases and almost 450 thousand deaths. In this paper, computational studies were carried out to unveil the catalytic mechanism of SHMT using QM/MM methodologies. This enzyme is responsible for the extraordinary cyclisation of a tetrahydrofolate (THF) into 5,10-methylene-THF. This process is catalyzed by a pyridoxal-5’-phosphate (PLP) cofactor that binds L-serine and from which one molecule of L-glycine is produced. The results show that the catalytic process takes place in eight sequential steps that involve an α-elimination, the cyclization of the 5-hydroxymethyl-THF intermediate into 5,10-methylene-THF and the protonation of the quinonoid intermediate. According to the calculated energetic profile, the rate-limiting step of the full mechanism is the elimination of the hydroxymethyl group, from which results a formaldehyde intermediate that then becomes covalently bonded to the THF cofactor. The calculated barrier (DLPNO-CCSD(T)/CBS:ff99SB) for the rate-limiting step (18.0 kcal/mol) agrees very well with the experimental kinetic results (15.7-16.2 kcal/mol). The results also highlight the key role played by Glu57 during the full catalytic process and particularly in the first step of the mechanism that requires an anionic Glu57, contrasting with some proposals available in the literature for this step. It was also concluded that the cyclisation of THF must take place in the enzyme, rather than in solution as it has been proposed also in the past. All of these results together provide new knowledge and insight on the catalytic mechanism of SHMT that now can be used to develop new inhibitors targeting SHMT and therefore new anti-malaria drugs.
Utilização de software na simulação molecular
Nuno Cerqueira, Sérgio Sousa, Henrique Fernandes e Carla Teixeira- Investigadores do DQB-FCUP
Conferência de especialidade
Dia 9 de Julho de 2018, 14h30
Auditório Grande do Centro Cultural Vila Flor
Maria João Ramos, Pedro Alexandrino Fernandes e Henrique Fernandes – Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto
Esta conferência de especialidade será dividida em três partes. Numa primeira palestra, eu próprio apresentarei alguns dos recursos digitais que temos vindo a desenvolver para o ensino da química, que permitem levar as Moléculas Magníficas para a sala de aula, no sentido de não só facilitar o processo de aprendizagem, mas também, e fundamentalmente, para despertar nos estudantes o fascínio pela química e pela ciência. Numa segunda palestra, o nosso convidado Henrique Fernandes (estudante de doutoramento na Univ. do Porto) fará uma apresentação sobre um conjunto de Moléculas Magníficas específicas, mostrando a sua explicando o seu papel na nossa vida. Por fim, numa terceira e última palestra, a Prof.a Maria João Ramos apresentará a história da iniciativa Moléculas Magníficas, o seu nascimento, as várias iniciativas de disseminação que têm vindo a ser feitas, as várias exposições, e os projetos futuros.
Entre as palestras terão lugar momentos de debate com a assembleia de participantes.
The molUP plugin, developed by Nuno Sousa Cerqueira and colleagues and described on page 1344, overcomes some of the most common problems in computational chemistry concerning the analysis of big data. MolUP was developed for use in the analysis of quantum chemistry (QM), QM/MM (molecular mechanics), and QM/QM calculations, molecular dynamics (MD) simulations, as well as the preparation of input files. MolUP also provides new tools to analyze and visualize existing computational chemistry information in a more userfriendly way that simplifies the current complex and time‐demanding practices used in the field. (DOI: 10.1002/jcc.25189)