Matches in SemOpenAlex for { <https://semopenalex.org/work/W1974411204> ?p ?o ?g. }
- W1974411204 endingPage "e26251" @default.
- W1974411204 startingPage "e26251" @default.
- W1974411204 abstract "Prolyl oligopeptidase (POP) is considered as an important pharmaceutical target for the treatment of numerous diseases. Despite enormous studies on various aspects of POPs structure and function still some of the questions are intriguing like conformational dynamics of the protein and interplay between ligand entry/egress. Here, we have used molecular modeling and docking based approaches to unravel questions like differences in ligand binding affinities in three POP species (porcine, human and A. thaliana). Despite high sequence and structural similarity, they possess different affinities for the ligands. Interestingly, human POP was found to be more specific, selective and incapable of binding to a few planar ligands which showed extrapolation of porcine POP in human context is more complicated. Possible routes for substrate entry and product egress were also investigated by detailed analyses of molecular dynamics (MD) simulations for the three proteins. Trajectory analysis of bound and unbound forms of three species showed differences in conformational dynamics, especially variations in β-propeller pore size, which was found to be hidden by five lysine residues present on blades one and seven. During simulation, β-propeller pore size was increased by ∼2 Å in porcine ligand-bound form which might act as a passage for smaller product movement as free energy barrier was reduced, while there were no significant changes in human and A. thaliana POPs. We also suggest that these differences in pore size could lead to fundamental differences in mode of product egress among three species. This analysis also showed some functionally important residues which can be used further for in vitro mutagenesis and inhibitor design. This study can help us in better understanding of the etiology of POPs in several neurodegenerative diseases." @default.
- W1974411204 created "2016-06-24" @default.
- W1974411204 creator A5076376082 @default.
- W1974411204 creator A5076779054 @default.
- W1974411204 date "2011-11-23" @default.
- W1974411204 modified "2023-09-29" @default.
- W1974411204 title "Structural Analysis of Prolyl Oligopeptidases Using Molecular Docking and Dynamics: Insights into Conformational Changes and Ligand Binding" @default.
- W1974411204 cites W1573122700 @default.
- W1974411204 cites W1764151989 @default.
- W1974411204 cites W1821584526 @default.
- W1974411204 cites W1848808867 @default.
- W1974411204 cites W1964370958 @default.
- W1974411204 cites W1965067620 @default.
- W1974411204 cites W1966041739 @default.
- W1974411204 cites W1968837049 @default.
- W1974411204 cites W1969398979 @default.
- W1974411204 cites W1970885638 @default.
- W1974411204 cites W1971746560 @default.
- W1974411204 cites W1974218649 @default.
- W1974411204 cites W1983981472 @default.
- W1974411204 cites W1984243890 @default.
- W1974411204 cites W1986191025 @default.
- W1974411204 cites W1990070939 @default.
- W1974411204 cites W1992192767 @default.
- W1974411204 cites W1995974096 @default.
- W1974411204 cites W1996550970 @default.
- W1974411204 cites W2008708467 @default.
- W1974411204 cites W2019030450 @default.
- W1974411204 cites W2020535330 @default.
- W1974411204 cites W2020689975 @default.
- W1974411204 cites W2026777107 @default.
- W1974411204 cites W2026868950 @default.
- W1974411204 cites W2035847639 @default.
- W1974411204 cites W2036700120 @default.
- W1974411204 cites W2036789309 @default.
- W1974411204 cites W2037184999 @default.
- W1974411204 cites W2037574006 @default.
- W1974411204 cites W2037990790 @default.
- W1974411204 cites W2051628563 @default.
- W1974411204 cites W2052067496 @default.
- W1974411204 cites W2058170527 @default.
- W1974411204 cites W2062224822 @default.
- W1974411204 cites W2065283382 @default.
- W1974411204 cites W2068621781 @default.
- W1974411204 cites W2068716401 @default.
- W1974411204 cites W2073920978 @default.
- W1974411204 cites W2074253762 @default.
- W1974411204 cites W2075814487 @default.
- W1974411204 cites W2076403167 @default.
- W1974411204 cites W2077776336 @default.
- W1974411204 cites W2082187825 @default.
- W1974411204 cites W2082628662 @default.
- W1974411204 cites W2086104408 @default.
- W1974411204 cites W2086716955 @default.
- W1974411204 cites W2088056472 @default.
- W1974411204 cites W2100091027 @default.
- W1974411204 cites W2106882534 @default.
- W1974411204 cites W2109827218 @default.
- W1974411204 cites W2109955285 @default.
- W1974411204 cites W2114367386 @default.
- W1974411204 cites W2122797035 @default.
- W1974411204 cites W2123768693 @default.
- W1974411204 cites W2139042499 @default.
- W1974411204 cites W2142209403 @default.
- W1974411204 cites W2142529984 @default.
- W1974411204 cites W2145914729 @default.
- W1974411204 cites W2147809382 @default.
- W1974411204 cites W2157492674 @default.
- W1974411204 cites W2158714788 @default.
- W1974411204 cites W2158888521 @default.
- W1974411204 cites W2168535596 @default.
- W1974411204 cites W2168770860 @default.
- W1974411204 cites W2312514959 @default.
- W1974411204 cites W2412251503 @default.
- W1974411204 cites W2949330193 @default.
- W1974411204 cites W4381544074 @default.
- W1974411204 cites W4385851958 @default.
- W1974411204 doi "https://doi.org/10.1371/journal.pone.0026251" @default.
- W1974411204 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3223163" @default.
- W1974411204 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22132071" @default.
- W1974411204 hasPublicationYear "2011" @default.
- W1974411204 type Work @default.
- W1974411204 sameAs 1974411204 @default.
- W1974411204 citedByCount "28" @default.
- W1974411204 countsByYear W19744112042012 @default.
- W1974411204 countsByYear W19744112042013 @default.
- W1974411204 countsByYear W19744112042014 @default.
- W1974411204 countsByYear W19744112042015 @default.
- W1974411204 countsByYear W19744112042017 @default.
- W1974411204 countsByYear W19744112042019 @default.
- W1974411204 countsByYear W19744112042020 @default.
- W1974411204 countsByYear W19744112042021 @default.
- W1974411204 countsByYear W19744112042022 @default.
- W1974411204 countsByYear W19744112042023 @default.
- W1974411204 crossrefType "journal-article" @default.
- W1974411204 hasAuthorship W1974411204A5076376082 @default.
- W1974411204 hasAuthorship W1974411204A5076779054 @default.
- W1974411204 hasBestOaLocation W19744112041 @default.