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Rational Enzyme Engineering Through Biophysical and Biochemical Modeling
dc.contributor.author | Acebes, Sandra |
dc.contributor.author | Fernández-Fueyo, Elena |
dc.contributor.author | Monza, Emanuele |
dc.contributor.author | Lucas, Fatima |
dc.contributor.author | Almendral, David |
dc.contributor.author | Ruiz-Dueñas, Fracisco J. |
dc.contributor.author | Lund, Henrik |
dc.contributor.author | Martínez, Ángel T. |
dc.contributor.author | Guallar, Víctor |
dc.contributor.other | Barcelona Supercomputing Center |
dc.date.accessioned | 2016-03-14T16:39:39Z |
dc.date.available | 2017-02-04T01:30:27Z |
dc.date.issued | 2016-02-03 |
dc.identifier.citation | Acebes, Sandra [et al.]. Rational Enzyme Engineering Through Biophysical and Biochemical Modeling. "ACS Catalysis", 03 Febrer 2016, vol. 6, núm. 3, p. 1624-1629. |
dc.identifier.issn | 2155-5435 |
dc.identifier.uri | http://hdl.handle.net/2117/84341 |
dc.description.abstract | Due to its importance in the pharmaceutical industry, ligand dynamic simulations have experienced a great expansion. Using all-atom models and cutting edge hardware, one can perform non-biased ligand migration, active site search and binding studies. In this letter we demonstrate (and validate by PCR mutagenesis) how these techniques, when combined with quantum mechanics, open new possibilities in enzyme engineering. We provide a complete analysis where: 1) biophysical simulations produce ligand diffusion and, 2) biochemical modeling samples the chemical event. Using such broad analysis we engineer a highly stable peroxidase activating the enzyme for new substrate oxidation after rational mutation of two non-conserved surface residues. In particular, we create a new surface-binding site, quantitatively predicting the in vitro change in oxidation rate obtained by mutagenic PCR and achieving a comparable specificity constant to active peroxidases. |
dc.description.sponsorship | This work was supported by the INDOX (KBBE-2013-7-613549 to ATM) European project, and the CTQ2013-48287 (to VG) and BIO2014-56388-R (to FJR-D) projects of the Spanish Ministry of Economy and Competitiveness (MINECO). FJR-D acknowledges a MINECO Ramón&Cajal contract. |
dc.format.extent | 6 p. |
dc.language.iso | eng |
dc.publisher | ACS Publications |
dc.subject | Àrees temàtiques de la UPC::Enginyeria mecànica::Impacte ambiental |
dc.subject.lcsh | Protein |
dc.subject.lcsh | Enzymes |
dc.subject.other | Protein engineering |
dc.subject.other | PELE |
dc.subject.other | Oxidases |
dc.subject.other | Manganese peroxidase |
dc.subject.other | Enzyme design |
dc.title | Rational Enzyme Engineering Through Biophysical and Biochemical Modeling |
dc.type | Article |
dc.subject.lemac | Proteïnes |
dc.subject.lemac | Enzims |
dc.identifier.doi | 10.1021/acscatal.6b00028 |
dc.description.peerreviewed | Peer Reviewed |
dc.relation.publisherversion | http://pubs.acs.org/doi/abs/10.1021/acscatal.6b00028 |
dc.rights.access | Open Access |
dc.description.version | Postprint (author's final draft) |
dc.relation.projectid | info:eu-repo/grantAgreement/EC/FP7/613549/EU/Optimized oxidoreductases for medium and large scale industrial biotransformations/INDOX |
dc.relation.projectid | info:eu-repo/grantAgreement/MINECO//CTQ2013-48287-R/ES/DISENYO COMPUTACIONAL RACIONAL DE OXIDOREDUCTASAS PARA APLICACIONES INDUSTRIALES Y TECNOLOGICAS/ |
dc.relation.projectid | info:eu-repo/grantAgreement/MINECO//BIO2014-56388-R/ES/NUEVAS ENZIMAS OXIDATIVAS PARA UNA INDUSTRIA SOSTENIBLE/ |
local.citation.publicationName | ACS Catalysis |
local.citation.volume | 6 |
local.citation.number | 3 |
local.citation.startingPage | 1624 |
local.citation.endingPage | 1629 |
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