Structural insights into the allosteric site of Arabidopsis NADP-malic enzyme 2: role of the second sphere residues in the regulatory signal transmission

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dc.citation.titlePlant Molecular Biologyes
dc.citation.volume107
dc.creatorGerrard Wheeler, Mariel Claudia
dc.creatorArias, Cintia Lucía
dc.creatorDa Fonseca Rezende e Mello, Juliana
dc.creatorCirauqui Diaz, Nuria
dc.creatorRodrigues, Carlos Rangel
dc.creatorDrincovich, María Fabiana
dc.creatorMendonça Teles de Souza, Alessandra
dc.creatorÁlvarez, Clarisa Ester
dc.date.accessioned2022-04-07T17:00:47Z
dc.date.available2022-04-07T17:00:47Z
dc.date.issued2021-07-31
dc.descriptionStructure–function studies contribute to deciphering how small modifcations in the primary structure could introduce desirable characteristics into enzymes without afecting its overall functioning. Malic enzymes (ME) are ubiquitous and responsible for a wide variety of functions. The availability of a high number of ME crystal structures from diferent species facilitates comparisons between sequence and structure. Specifcally, the structural determinants necessary for fumarate allosteric regulation of ME has been of particular interest. NADP-ME2 from Arabidopsis thaliana exhibits a distinctive and complex regulation by fumarate, acting as an activator or an inhibitor according to substrate and efector concentrations. However, the 3D structure for this enzyme is not yet reported. In this work, we characterized the NADP-ME2 allosteric site by structural modeling, molecular docking, normal mode analysis and mutagenesis. The regulatory site model and its docking analysis suggested that other C4 acids including malate, NADP-ME2 substrate, could also ft into fumarate’s pocket. Besides, a non-conserved cluster of hydrophobic residues in the second sphere of the allosteric site was identifed. The substitution of one of those residues, L62, by a less fexible residue as tryptophan, resulted in a complete loss of fumarate activation and a reduction of substrate afnities for the active site. In addition, normal mode analysis indicated that conformational changes leading to the activation could originate in the region surrounding L62, extending through the allosteric site till the active site. Finally, the results in this work contribute to the understanding of structural determinants necessary for allosteric regulation providing new insights for enzyme optimization.es
dc.description.filFil: Gerrard Wheeler, Mariel Claudia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos (CEFOBI-CONICET); Argentina.es
dc.description.filFil: Arias, Cintia Lucía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos (CEFOBI-CONICET); Argentina.es
dc.description.filFil: Da Fonseca Rezende e Mello, Juliana. Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Laboratório de Modelagem Molecular & QSAR (ModMolQSAR); Brazil.es
dc.description.filFil: Cirauqui Diaz, Nuria. Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Laboratório de Modelagem Molecular & QSAR (ModMolQSAR); Brazil.es
dc.description.filFil: Rodrigues, Carlos Rangel. Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Laboratório de Modelagem Molecular & QSAR (ModMolQSAR); Brazil.es
dc.description.filFil: Drincovich, María Fabiana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos (CEFOBI-CONICET); Argentina.es
dc.description.filFil: Mendonça Teles de Souza, Alessandra. Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Laboratório de Modelagem Molecular & QSAR (ModMolQSAR); Brazil.es
dc.description.filFil: Alvarez, Clarisa Ester. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos (CEFOBI-CONICET); Argentina.es
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.description.sponsorshipFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ): Number E-26/203.179/2016.
dc.formatapplication/pdf
dc.format.extent37-48es
dc.identifier.issn1573-5028es
dc.identifier.urihttp://hdl.handle.net/2133/23339
dc.language.isoenges
dc.publisherSpringeres
dc.relation.publisherversionhttps://doi.org/10.1007/s11103-021-01176-2
dc.relation.publisherversionhttps://link.springer.com/article/10.1007/s11103-021-01176-2
dc.rightsopenAccesses
dc.rights.holderGerrard Wheeler, Mariel Claudiaes
dc.rights.holderArias, Cintia Lucíaes
dc.rights.holdere Mello da Fonseca Rezende, Julianaes
dc.rights.holderCirauqui Diaz, Nuriaes
dc.rights.holderRodrigues, Carlos Rangeles
dc.rights.holderDrincovich, María Fabianaes
dc.rights.holderde Souza Mendonça Teles, Alessandraes
dc.rights.holderÁlvarez, Clarisa Esteres
dc.rights.textAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)es
dc.subjectMalic enzymees
dc.subjectFumarate regulationes
dc.subjectStructure–functiones
dc.titleStructural insights into the allosteric site of Arabidopsis NADP-malic enzyme 2: role of the second sphere residues in the regulatory signal transmissiones
dc.typepublishedVersion
dc.typearticle
dc.typeartículo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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