BioComp group project

StopProt Project 

Protein synthesis and protein degradation are two universal complementary processes, permanently occurring in a living cell. Protein backbones are very stable in water at neutral pH and room temperature. The half-life of a peptide bond under normal conditions can range from 7 years to 600 years, even higher for peptides protected by modified terminus or within the protein interior.  But there is a group of enzymes, the proteases, whose catalytic function is to hydrolyse peptide bonds with very high efficiency.

   The view of proteases has come a long way since P. A. Levene reported his studies on “The Cleavage Products of Proteases” in the first issue of The Journal of Biological Chemistry published October 1, 1905. Today, after more than 100 years and more than 350,000 articles on these enzymes in the scientific literature, proteases remain at the cutting edge of biological research.

Project Leader: Dr. Katarzyna Świderek

   Proteases are classified based on their mode of action and biocatalytic mechanisms. Natural and modified commercial proteases are produced with applications in detergents, leather, food processing, and medicine. They are also used as biocatalysts in organic synthesis. Proteases are present in all organisms where they participate in most aspects of cell nutrition, physiology, regulation, and in microbial pathogenesis.

Depending on their site of action, proteases are categorized into two major groups: exoproteases and endoproteases. Further classification relies on the distinct arrangement of functional groups present at the active site of the enzyme. Non-metal proteases are subdivided into five different subgroups: cysteine, aspartate, serine, glutamic acid and threonine proteases. The physiological roles of proteases are very diverse, participating in a wide range of molecular and cellular activities, including from digestive functions, the removal of damaged proteins, and protein maturation to the precise processing of regulatory proteins.


Just Published:

L. Williams, I.M. Taily, L Hatton, A.A. Berezin, Y.L. Wu, V. Moliner, K. Świderek*, Y. Tsai*, L.Y.P Luk* "Secondary Amine Catalysis in Enzyme Design: Broadening Protein Template Diversity through Genetic Code Expansion" Angew. Chemie Int. Ed. e202403098 (2024) DOI:10.1002/ange.202403098

K. Świderek*, S. Marti, K. Arafet, V. Moliner* "Computational study of the Mechanism of a polyurethane esterase A (PueA) from Pseudomonas chlororaphisFaraday Discussions Accepted Manuscript (2024) DOI: 10.1039/D4FD00022F

J.J. Ruiz-Pernía, K. Świderek, J. Bertran, V. Moliner, I. Tuñón "Electrostatics as a Guiding Principle in Understanding and Designing Enzymes" J. Chem. Theory Comput. 20, 1783 (2024) DOI:10.1021/acs.jctc.3c01395

E. Gabirondo, K. Świderek, E. Marin, A. Maiz-Iginitz, A. Larranaga, V. Moliner, A. Etxeberria, H. Sardon "A Single Amino Acid Able to Promote High-Temperature Ring-Opening Polymerization by Dual Activation" Adv. Sci., 2308956 (2024) DOI: 10.1002/advs.202308956

K. Świderek*, S. Velasco-Lozano, M. À. Galmés, I. Olazabal, H. Sardon, F. López-Gallego*, V. Moliner* "Mechanistic studies of a lipase unveil effect of pH on hydrolysis products of small PET modules" Nat. Commun. 14:3556. (2023) doi: 10.1038/s41467-023-39201-1

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COVID-19 project:


S. Martí, K. Arafet, A. Lodola, A. J. Mulholland, K. Świderek*, V. Moliner* ACS Catal. 12, 1, 698–708 (2022) doi: 10.1021/acscatal.1c04661


S. Martí, K. Arafet, A. Lodola, A. J. Mulholland, K. Świderek*, V. Moliner*  ACS Catal. 12, 1, 698–708 (2022) doi: 10.1021/acscatal.1c04661


H.T.H. Chan, M.A. Moesser, R.K. Walters, T.R. Malla, R.M. Twidale, T. John, H.M. Deeks, T. Johnston-Wood, V. Mikhailov, R.B. Sessions, W. Dawson, E. Saleh, P. Lukacik, C. Strain-Damerell, C.D. Owen, T. Nakajima, K. Świderek, A. Lodola, V. Moliner, D.R. Glowacki, J. Spencer, M.A.A. Walsh, C.J. Schofield, L. Genovese, D.K. Shoemark, A.J. Mulholland, F. Duarte, G.M. Morris  Chem. Sci. 12, 13686-13703 (2021) doi:10.1039/D1SC03628A


K. Arafet, N. Serrano-Aparicio A. Lodola A. Mulholland, F. V. González, K. Świderek*, V. Moliner* Chem. Sci. 12, 1433-1444 (2021) ChemRxiv Preprint Doi: 10.26434/chemrxiv.12941819.v1


K. Świderek*V. Moliner* Chem. Sci. 11, 10626-10630 (2020) ChemRxiv Preprint Doi: 10.26434/Chemrxiv.12283967.V1 2020 Chemical Science HOT Article Collection And Celebrating 10 Years Of Chemical Science