Academic Journal
Heme-binding enables allosteric modulationin an ancient TIM-barrel glycosidase
| العنوان: | Heme-binding enables allosteric modulationin an ancient TIM-barrel glycosidase |
|---|---|
| المؤلفون: | Gamiz-Arco, Gloria, Gutierrez-Rus, Luis I., Risso, Valeria A., Ibarra-Molero, Beatriz, Hoshino, Yosuke, Petrović, Dušan, Justicia, Jose, Cuerva, Juan Manuel, Romero-Rivera, Adrian, Seelig, Burckhard, Gavira, Jose A., Kamerlin, Shina C.L., Gaucher, Eric A., Sánchez-Ruiz, Jose M. |
| المساهمون: | Ministerio de Economía y Competitividad (España) |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2021 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| الوصف: | Glycosidases are phylogenetically widely distributed enzymes that are crucial for the cleavage of glycosidic bonds. Here, we present the exceptional properties of a putative ancestor of bacterial and eukaryotic family-1 glycosidases. The ancestral protein shares the TIM-barrel fold with its modern descendants but displays large regions with greatly enhanced conformational flexibility. Yet, the barrel core remains comparatively rigid and the ancestral glycosidase activity is stable, with an optimum temperature within the experimental range for thermophilic family-1 glycosidases. None of the ∼5500 reported crystallographic structures of ∼1400 modern glycosidases show a bound porphyrin. Remarkably, the ancestral glycosidase binds heme tightly and stoichiometrically at a well-defined buried site. Heme binding rigidifies this TIM-barrel and allosterically enhances catalysis. Our work demonstrates the capability of ancestral protein reconstructions to reveal valuable but unexpected biomolecular features when sampling distant sequence space. The potential of the ancestral glycosidase as a scaffold for custom catalysis and biosensor engineering is discussed. ; This work was supported by Human Frontier Science Program Grant RGP0041 (J.M.S.-R., E.A.G., B.S., and S.C.L.K.), NIH grant R01AR069137 (E.A.G.), Department of Defense grant MURI W911NF-16-1-0372 (E.A.G.), the Swedish Research Council (2019-03499) (S.C.L.K.), the Knut and Alice Wallenberg Foundation (2018.0140 and 2019.0431) (S.C.L.K.), Spanish Ministry of Economy and Competitiveness/FEDER Funds Grants BIO2015-66426-R (J.M.S.-R.) RTI2018-097142-B-100 (J.M.S.-R.) and BIO2016-74875-P (J.A.G.). The simulations were enabled by resources provided by the Swedish National Infrastructure for Computing (SNIC) at UPPMAX partially funded by the Swedish Research Council through grant agreement no. 2016-07213. We acknowledge the Spanish Synchrotron Radiation Facility (ALBA, Barcelona) for the provision of synchrotron radiation facilities and the staff at XALOC beamline for ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 2041-1723 |
| Relation: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/MINECO//BIO2015-66426-R; info:eu-repo/grantAgreement/MINECO//BIO2016-74875-P; info:eu-repo/grantAgreement/MINECO//RTI2018-097142-B-100; Publisher's version; http://dx.doi.org/10.1038/s41467-020-20630-1; Sí; Nature Communications 12 (2021); http://hdl.handle.net/10261/278113; http://dx.doi.org/10.13039/501100003329 |
| DOI: | 10.1038/s41467-020-20630-1 |
| DOI: | 10.13039/501100003329 |
| الاتاحة: | http://hdl.handle.net/10261/278113 https://doi.org/10.1038/s41467-020-20630-1 https://doi.org/10.13039/501100003329 |
| Rights: | open |
| رقم الانضمام: | edsbas.68F4E3E6 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20411723 |
|---|---|
| DOI: | 10.1038/s41467-020-20630-1 |