A5064545978- Protein Structure and Dynamics
- Enzyme Structure and Function
- Cellular transport and secretion
- Cancer-related gene regulation
- Trypanosoma species research and implications
- Pancreatitis Pathology and Treatment
- Insect and Pesticide Research
- Complement system in diseases
- Insect Resistance and Genetics
- Bacteriophages and microbial interactions
- Protease and Inhibitor Mechanisms
Eötvös Loránd University
2022-2025
HUN-REN Research Centre for Natural Sciences
2023-2024
Hungarian Research Network
2023-2024
Institute of Molecular Life Sciences
2023
Renal ischemia–reperfusion injury (IRI) is a common complication in several clinical scenarios including kidney transplantation. Mannan-binding lectin-associated serine proteinase (MASP)-2 essential for activation of the complement lectin pathway, which has been implicated pathogenesis renal IRI and therefore represents potential therapeutic target. We developed new, affinity-enhanced MASP-2 inhibitor, EVO24, by directed evolution D2 domain human tissue factor pathway inhibitor. EVO24 was...
Abstract Canonical serine protease inhibitor proteins occupy the substrate‐binding groove of their target enzyme via a surface loop. Unlike true substrates, inhibitors are cleaved by extremely slowly. Here, we applied an unbiased directed evolution approach to investigate which loop residues hamper proteolytic cleavage while maintaining high‐affinity binding. As model system, used human chymotrypsin C (CTRC) and Schistocerca gregaria 2 (SGPI‐2). We created SGPI‐2 library displayed on M13...
Chymotrypsin-like protease (CTRL) is one of the four chymotrypsin isoforms expressed in human exocrine pancreas. Human genetic and experimental evidence indicate that chymotrypsins B1, B2, C (CTRB1, CTRB2 CTRC) are important not only for protein digestion but also protecting pancreas against pancreatitis by degrading potentially harmful trypsinogen. CTRL has been reported to play a similar role, possibly due its low abundance and/or different substrate specificity. To address this problem,...
Pancreatic chymotrypsins (CTRs) are digestive proteases that in humans include CTRB1, CTRB2, CTRC, and CTRL. The highly similar CTRB1 CTRB2 the products of gene duplication. A common inversion at CTRB1-CTRB2 locus reverses expression ratio these isoforms favor CTRB2. Carriers allele protected against inflammatory disorder pancreatitis presumably via their increased capacity for CTRB2-mediated degradation harmful trypsinogen. To reveal protective molecular determinants we compared enzymatic...
ABSTRACT Eglin C, a small protein from the medicinal leech, has been long considered general high‐affinity inhibitor of chymotrypsins and elastases. Here, we demonstrate that eglin C inhibits human chymotrypsin‐like protease (CTRL) weaker by several orders magnitude than other chymotrypsins. In order to identify underlying structural aspects this unique deviation, performed comparative molecular dynamics simulations on experimental AlphaFold model structures bovine CTRA CTRL. Our results...
While the majority of proteins with available structures are able to fold independently and mediate interactions only after acquiring their folded state, a subset known protein complexes contains chains that intrinsically disordered in isolation. The Mutual Folding Induced by Binding (MFIB) database collects classifies complexes, wherein all constituent would be unstable/disordered isolation but into well-defined 3D complex structure upon binding. This phenomenon is often termed as...
Mutual synergistic folding (MSF) proteins belong to a recently emerged subclass of disordered proteins, which are in their monomeric forms but become ordered oligomeric forms. They can be identified by experimental methods following unfolding, happens single-step cooperative process, without the presence stable intermediates. Only limited number experimentally validated MSF accessible. The amino acid composition shows high similarity globular rather than ones. However, they have some special...