Structure, Oligomerization and Activity Modulation in N-Ribohydrolases
Enzymes catalyzing the hydrolysis of the N-glycosidic bond in nucleosides and other ribosides (N-ribohydrolases, NHs) with diverse substrate specificities are found in all kingdoms of life. While the overall NH fold is highly conserved, limited substitutions and insertions can account for difference...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/5/2576 |
| _version_ | 1797474986690084864 |
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| author | Massimo Degano |
| author_facet | Massimo Degano |
| author_sort | Massimo Degano |
| collection | DOAJ |
| description | Enzymes catalyzing the hydrolysis of the N-glycosidic bond in nucleosides and other ribosides (N-ribohydrolases, NHs) with diverse substrate specificities are found in all kingdoms of life. While the overall NH fold is highly conserved, limited substitutions and insertions can account for differences in substrate selection, catalytic efficiency, and distinct structural features. The NH structural module is also employed in monomeric proteins devoid of enzymatic activity with different physiological roles. The homo-oligomeric quaternary structure of active NHs parallels the different catalytic strategies used by each isozyme, while providing a buttressing effect to maintain the active site geometry and allow the conformational changes required for catalysis. The unique features of the NH catalytic strategy and structure make these proteins attractive targets for diverse therapeutic goals in different diseases. |
| first_indexed | 2024-03-09T20:37:44Z |
| format | Article |
| id | doaj.art-3ba70482cd614e20ab0f884248ce3604 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:37:44Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3ba70482cd614e20ab0f884248ce36042023-11-23T23:06:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01235257610.3390/ijms23052576Structure, Oligomerization and Activity Modulation in N-RibohydrolasesMassimo Degano0Biocrystallography Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS Scientific Institute San Raffaele, via Olgettina 60, 20132 Milano, ItalyEnzymes catalyzing the hydrolysis of the N-glycosidic bond in nucleosides and other ribosides (N-ribohydrolases, NHs) with diverse substrate specificities are found in all kingdoms of life. While the overall NH fold is highly conserved, limited substitutions and insertions can account for differences in substrate selection, catalytic efficiency, and distinct structural features. The NH structural module is also employed in monomeric proteins devoid of enzymatic activity with different physiological roles. The homo-oligomeric quaternary structure of active NHs parallels the different catalytic strategies used by each isozyme, while providing a buttressing effect to maintain the active site geometry and allow the conformational changes required for catalysis. The unique features of the NH catalytic strategy and structure make these proteins attractive targets for diverse therapeutic goals in different diseases.https://www.mdpi.com/1422-0067/23/5/2576ribosidesN-ribohydrolasesstructural enzymologyquaternary structuredrug design |
| spellingShingle | Massimo Degano Structure, Oligomerization and Activity Modulation in N-Ribohydrolases International Journal of Molecular Sciences ribosides N-ribohydrolases structural enzymology quaternary structure drug design |
| title | Structure, Oligomerization and Activity Modulation in N-Ribohydrolases |
| title_full | Structure, Oligomerization and Activity Modulation in N-Ribohydrolases |
| title_fullStr | Structure, Oligomerization and Activity Modulation in N-Ribohydrolases |
| title_full_unstemmed | Structure, Oligomerization and Activity Modulation in N-Ribohydrolases |
| title_short | Structure, Oligomerization and Activity Modulation in N-Ribohydrolases |
| title_sort | structure oligomerization and activity modulation in n ribohydrolases |
| topic | ribosides N-ribohydrolases structural enzymology quaternary structure drug design |
| url | https://www.mdpi.com/1422-0067/23/5/2576 |
| work_keys_str_mv | AT massimodegano structureoligomerizationandactivitymodulationinnribohydrolases |