Local frustration around enzyme active sites
Conflicting biological goals often meet in the specification of protein sequences for structure and function. Overall, strong energetic conflicts are minimized in folded native states according to the principle of minimal frustration, so that a sequence can spontaneously fold, but local violations o...
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2019
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v116_n10_p4037_Freiberger http://hdl.handle.net/20.500.12110/paper_00278424_v116_n10_p4037_Freiberger |
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paper:paper_00278424_v116_n10_p4037_Freiberger2023-06-08T14:54:35Z Local frustration around enzyme active sites Bioinformatics Catalytic sites Evolution Local frustration Protein enzymes article bioinformatics catalysis enzyme active site enzyme activity frustration oligomerization Conflicting biological goals often meet in the specification of protein sequences for structure and function. Overall, strong energetic conflicts are minimized in folded native states according to the principle of minimal frustration, so that a sequence can spontaneously fold, but local violations of this principle open up the possibility to encode the complex energy landscapes that are required for active biological functions. We survey the local energetic frustration patterns of all protein enzymes with known structures and experimentally annotated catalytic residues. In agreement with previous hypotheses, the catalytic sites themselves are often highly frustrated regardless of the protein oligomeric state, overall topology, and enzymatic class. At the same time a secondary shell of more weakly frustrated interactions surrounds the catalytic site itself. We evaluate the conservation of these energetic signatures in various family members of major enzyme classes, showing that local frustration is evolutionarily more conserved than the primary structure itself. © 2019 National Academy of Sciences. All Rights Reserved. 2019 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v116_n10_p4037_Freiberger http://hdl.handle.net/20.500.12110/paper_00278424_v116_n10_p4037_Freiberger |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Bioinformatics Catalytic sites Evolution Local frustration Protein enzymes article bioinformatics catalysis enzyme active site enzyme activity frustration oligomerization |
| spellingShingle |
Bioinformatics Catalytic sites Evolution Local frustration Protein enzymes article bioinformatics catalysis enzyme active site enzyme activity frustration oligomerization Local frustration around enzyme active sites |
| topic_facet |
Bioinformatics Catalytic sites Evolution Local frustration Protein enzymes article bioinformatics catalysis enzyme active site enzyme activity frustration oligomerization |
| description |
Conflicting biological goals often meet in the specification of protein sequences for structure and function. Overall, strong energetic conflicts are minimized in folded native states according to the principle of minimal frustration, so that a sequence can spontaneously fold, but local violations of this principle open up the possibility to encode the complex energy landscapes that are required for active biological functions. We survey the local energetic frustration patterns of all protein enzymes with known structures and experimentally annotated catalytic residues. In agreement with previous hypotheses, the catalytic sites themselves are often highly frustrated regardless of the protein oligomeric state, overall topology, and enzymatic class. At the same time a secondary shell of more weakly frustrated interactions surrounds the catalytic site itself. We evaluate the conservation of these energetic signatures in various family members of major enzyme classes, showing that local frustration is evolutionarily more conserved than the primary structure itself. © 2019 National Academy of Sciences. All Rights Reserved. |
| title |
Local frustration around enzyme active sites |
| title_short |
Local frustration around enzyme active sites |
| title_full |
Local frustration around enzyme active sites |
| title_fullStr |
Local frustration around enzyme active sites |
| title_full_unstemmed |
Local frustration around enzyme active sites |
| title_sort |
local frustration around enzyme active sites |
| publishDate |
2019 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v116_n10_p4037_Freiberger http://hdl.handle.net/20.500.12110/paper_00278424_v116_n10_p4037_Freiberger |
| _version_ |
1768545866020290560 |