Fuxreiter M

References (2)

Title : Adventures on the routes of protein evolution - in memoriam Dan Salah Tawfik (1955 - 2021) - Jackson_2022_J.Mol.Biol_434_167462
Author(s) : Jackson C , Toth-Petroczy A , Kolodny R , Hollfelder F , Fuxreiter M , Caroline Lynn Kamerlin S , Tokuriki N
Ref : Journal of Molecular Biology , :167462 , 2022
Abstract : Understanding how proteins evolved not only resolves mysteries of the past, but also helps address challenges of the future, particularly those relating to the design and engineering of new protein functions. Here we review the work of Dan S. Tawfik, one of the pioneers of this area, highlighting his seminal contributions in diverse fields such as protein design, high throughput screening, protein stability, fundamental enzyme-catalyzed reactions and promiscuity, that underpin biology and the origins of life. We discuss the influence of his work on how our models of enzyme and protein function have developed and how the main driving forces of molecular evolution were elucidated. The discovery of the rugged routes of evolution has enabled many practical applications, some which are now widely used.
ESTHER : Jackson_2022_J.Mol.Biol_434_167462
PubMedSearch : Jackson_2022_J.Mol.Biol_434_167462
PubMedID: 35104498

Title : Flexibility of prolyl oligopeptidase: molecular dynamics and molecular framework analysis of the potential substrate pathways - Fuxreiter_2005_Proteins_60_504
Author(s) : Fuxreiter M , Magyar C , Juhasz T , Szeltner Z , Polgar L , Simon I
Ref : Proteins , 60 :504 , 2005
Abstract : The flexibility of prolyl oligopeptidase has been investigated using molecular dynamics (MD) and molecular framework approaches to delineate the route of the substrate to the active site. The selectivity of the enzyme is mediated by a seven-bladed beta-propeller that in the crystal structure does not indicate the possible passage for the substrate to the catalytic center. Its open topology however, could allow the blades to move apart and let the substrate into the large central cavity. Flexibility analysis of prolyl oligopeptidase structure using the FIRST (Floppy Inclusion and Rigid Substructure Topology) approach and the atomic fluctuations derived from MD simulations demonstrated the rigidity of the propeller domain, which does not permit the substrate to approach the active site through this domain. Instead, a smaller tunnel at the inter-domain region comprising the highly flexible N-terminal segment of the peptidase domain and a facing hydrophilic loop from the propeller (residues 192-205) was identified by cross-correlation analysis and essential dynamics as the only potential pathway for the substrate. The functional importance of the flexible loop has been also verified by kinetic analysis of the enzyme with a split loop. Catalytic effect of engineered disulfide bridges was rationalized by characterizing the concerted motions of the two domains.
ESTHER : Fuxreiter_2005_Proteins_60_504
PubMedSearch : Fuxreiter_2005_Proteins_60_504
PubMedID: 15971204