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Electric Field Measurements Reveal the Pivotal Role of Cofactor–Substrate Interaction in Dihydrofolate Reductase Catalysis
dc.contributor.author | Adesina, Aduragbemi S. | |
dc.contributor.author | Świderek, Katarzyna | |
dc.contributor.author | Luk, Louis Y. P. | |
dc.contributor.author | Moliner, Vicent | |
dc.date.accessioned | 2020-11-04T08:04:17Z | |
dc.date.available | 2020-11-04T08:04:17Z | |
dc.date.issued | 2020-07-17 | |
dc.identifier.citation | Adesina, A. S.; Świderek, K.; Luk, L. Y.; Moliner, V.; Allemann, R. K.. Electric Field Measurements Reveal the Pivotal Role of Cofactor–Substrate Interaction in Dihydrofolate Reductase Catalysis ACS Catalysis 2020 10 (14), 7907-7914 DOI: 10.1021/acscatal.0c01856 | ca_CA |
dc.identifier.issn | 2155-5435 | |
dc.identifier.uri | http://hdl.handle.net/10234/190215 | |
dc.description.abstract | The contribution of ligand–ligand electrostatic interaction to transition state formation during enzyme catalysis has remained unexplored, even though electrostatic forces are known to play a major role in protein functions and have been investigated by the vibrational Stark effect (VSE). To monitor electrostatic changes along important steps during catalysis, we used a nitrile probe (T46C-CN) inserted proximal to the reaction center of three dihydrofolate reductases (DHFRs) with different biophysical properties, Escherichia coli DHFR (EcDHFR), its conformationally impaired variant (EcDHFR-S148P), and Geobacillus stearothermophilus DHFR (BsDHFR). Our combined experimental and computational approach revealed that the electric field projected by the substrate toward the probe negates those exerted by the cofactor when both are bound within the enzymes. This indicates that compared to previous models that focus exclusively on subdomain reorganization and protein–ligand contacts, ligand–ligand interactions are the key driving force to generate electrostatic environments conducive for catalysis. | ca_CA |
dc.format.extent | 8 p. | ca_CA |
dc.format.mimetype | application/pdf | ca_CA |
dc.language.iso | eng | ca_CA |
dc.publisher | American Chemical Society | ca_CA |
dc.relation.isPartOf | ACS catalysis, 2020, vol. 10, no 14 | ca_CA |
dc.rights | This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. | ca_CA |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | * |
dc.subject | dihydrofolate reductase | ca_CA |
dc.subject | vibrational Stark effect | ca_CA |
dc.subject | protein FTIR | ca_CA |
dc.subject | protein dynamics | ca_CA |
dc.subject | protein electrostatic | ca_CA |
dc.subject | ligand−ligand interaction | ca_CA |
dc.title | Electric Field Measurements Reveal the Pivotal Role of Cofactor–Substrate Interaction in Dihydrofolate Reductase Catalysis | ca_CA |
dc.type | info:eu-repo/semantics/article | ca_CA |
dc.identifier.doi | https://doi.org/10.1021/acscatal.0c01856 | |
dc.relation.projectID | MINECO: IJCI-201627503; Cardiff University; Biotechnology and Biological Sciences Research Council (BBSRC): BB/J005266, BB/L020394; Spanish Ministerio de Ciencia, Innovacion y Universidades: PGC2018-094852-B-C21; Generalitat Valenciana: AICO/2019/195; Universitat Jaume I: UJI~B2017-31 | ca_CA |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_CA |
dc.relation.publisherVersion | https://pubs.acs.org/doi/10.1021/acscatal.0c01856 | ca_CA |
dc.type.version | info:eu-repo/semantics/publishedVersion | ca_CA |
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