Publications
#Protein_Evolution #Protein_Engineering #Bioinfo #Bioremediation #InDels #Crystallography #Artificial _Intelligence
ORCID | Google Scholar
My research revolves around understanding fundamental principles of protein evolution. I employ X-ray crystallography to look into the atomic secrets of protein structures. By understanding how proteins naturally evolve, we can use that knowledge to create new proteins with custom-made properties for a wide range of biotechnological applications.
Molecular handcraft of a well‐folded protein chimera
In this work, we focused on the modular assembly approach to creating new proteins, leveraging information from protein engineering and natural evolution.
Specifically, we utilized the subdomain-database Fuzzle to construct a fold-chimera by integrating a flavodoxin-like fragment into a periplasmic binding protein. Our chimera exhibited strong folding characteristics, as evidenced by stable interfaces between the incorporated fragments observed in the crystal structure analysis. These results underscore the adaptability of α/β-proteins and represent a significant step towards optimization in protein engineering.
Insertions and deletions mediating the divergence of protein functions
In this study, we focused on understanding how the most catalytically-diverse enzymes (Rossmann enzymes) switch their coenzyme preferences.
Enzymes are the molecular machines that facilitate chemical reactions in our cells, and coenzymes are small molecules that help enzymes do their job. We removed three specific amino acids (the building blocks of proteins) from Rossmann enzymes to switch the binding of a redox coenzyne towards a methylating one. These findings demonstrate that enzymes likely explored distinct chemistries with minor changes in their amino acid sequences.
Mechanisms of protein evolution
How do proteins evolve? How do changes in sequence mediate changes in protein structure, and in turn in function?
This question has multiple angles, ranging from biochemistry and biophysics to evolutionary biology. In this review we provide a brief integrated view of some key mechanistic aspects of protein evolution.
Natural Building Blocks for Evolution-Guided Fragment-Based Protein Design
In this study we systematically searched for common fragments between proteins with distinct overall architecture, following the hypothesis that nature employed a “Lego-brick” strategy to build multiple architectures.
We discovered fragments that are present throughout the protein universe, appearing in diverse environments. Remarkably, we identified over a thousand sub-domain sized fragments that Nature has ingeniously repurposed to create new proteins. These fragments offer an exciting and innovative avenue for protein design. For easy access and further exploration, we have made our findings available to the public in the Fuzzle database, accessible at fuzzle.uni-bayreuth.de.
Insertions and deletions mediating changes in protein structure
In this study, we explored how different protein structures, evolved from common ancestors.
Proteins are made up of a limited number of building blocks, and their diverse functions and shapes come from combining these building blocks in various ways.
We discovered evidence suggesting that a specific protein fold, called HemD-like, emerged from another fold called flavodoxin-like, through a process involving gene duplication and segment swapping. To test our hypothesis, we reversed these evolutionary steps, recreating the flavodoxin-like shape from a HemD-half. This experimental result strongly supported our idea of a common ancestry for these two folds.
Divergence of methionine adenosyltransferase in archaea
Here we investigated an ancient enzyme called Methionine adenosyltransferase (MAT), responsible for producing a crucial molecule called S-adenosyl methionine in all living organisms.
While MAT enzymes are thought to have a common ancestor, the sequences in archaea showed significant differences compared to bacteria and eukaryotes.
By analyzing the structures and evolutionary history of these enzymes, we found that the archaeal MAT diverged notably, particularly in the active site where chemical reactions occur, showing how related enzymes can evolve notably different through the course of evolution.
Posters
Insertions and deletions mediating the divergence of protein functions