Why Are Some Enzymes Dimers? Flexibility and Catalysis in Thermotoga maritima Dihydrofolate Reductase
Impacto
Scholar |
Otros documentos de la autoría: Ruiz-Pernía, José Javier; Tuñón, Iñaki; Moliner, Vicent; Allemann, Rudolf K.
Metadatos
Mostrar el registro completo del ítemcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7013
comunitat-uji-handle3:10234/8638
comunitat-uji-handle4:
INVESTIGACIONMetadatos
Título
Why Are Some Enzymes Dimers? Flexibility and Catalysis in Thermotoga maritima Dihydrofolate ReductaseFecha de publicación
2019-05-13Editor
American Chemical SocietyISSN
2155-5435Cita bibliográfica
Ruiz-Pernía, J. Javier, Tuñón, Iñaki, Moliner, Vicent and Allemann, Rudolf K. 2019. Why are some enzymes dimers? flexibility and catalysis in Thermotoga maritima dihydrofolate reductase. ACS Catalysis 9 , pp. 5902-5911. 10.1021/acscatal.9b01250Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
https://pubs.acs.org/doi/abs/10.1021/acscatal.9b01250Versión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
Dihydrofolate reductase from Thermotoga maritima (TmDFHFR) is a dimeric thermophilic enzyme that catalyzes the hydride transfer from the cofactor NADPH to dihydrofolate less efficiently than other DHFR enzymes, such ... [+]
Dihydrofolate reductase from Thermotoga maritima (TmDFHFR) is a dimeric thermophilic enzyme that catalyzes the hydride transfer from the cofactor NADPH to dihydrofolate less efficiently than other DHFR enzymes, such as the mesophilic analogue Escherichia coli DHFR (EcDHFR). Using QM/MM potentials, we show that the reduced catalytic efficiency of TmDHFR is most likely due to differences in the amino acid sequence that stabilize the M20 loop in an open conformation, which prevents the formation of some interactions in the transition state and increases the number of water molecules in the active site. However, dimerization provides two advantages to the thermophilic enzyme: it protects its structure against denaturation by reducing thermal fluctuations and it provides a less negative activation entropy, toning down the increase of the activation free energy with temperature. Our molecular picture is confirmed by the analysis of the temperature dependence of enzyme kinetic isotope effects in different DHFR enzymes. [-]
Publicado en
ACS Catalysis, 2019, 9, 7, 5902-5911Proyecto de investigación
Spanish Ministerio de Economia y Competitividad and FEDER funds: PGC2018-094852-B-C2, CTQ2015-66223-C2, CTQ201S-74523-JIN(AEI/FEDER); Universitat Jaume I: UJI.B2017-31; Generalitat Valenciana: AICO/2018/238; United States Department of Health & Human Services National Institutes of Health (NIH) - USA: NIH R01 GM065368;Biotechnology and Biological Sciences Research Council (BBSRC): BB/J005266/1 BB/L020394/1Derechos de acceso
info:eu-repo/semantics/openAccess
Aparece en las colecciones
- QFA_Articles [817]
El ítem tiene asociados los siguientes ficheros de licencia: