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A comparative structural analysis reveals distinctive features of co-factor binding and substrate specificity in plant aldo-keto reductases.
Giuseppe, Priscila Oliveira de; Santos, Marcelo Leite Dos; Sousa, Sylvia Morais de; Koch, Karen E; Yunes, José Andrés; Aparicio, Ricardo; Murakami, Mario Tyago.
Afiliación
  • Giuseppe PO; Biosciences National Laboratory (LNBio), National Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil.
  • Santos MLD; Laboratory of Structural Biology and Crystallography, Institute of Chemistry, University of Campinas, Campinas, SP, Brazil.
  • Sousa SM; Embrapa Maize and Sorghum, Sete Lagoas, MG, Brazil.
  • Koch KE; Department of Horticultural Science, University of Florida, Gainesville, FL, USA.
  • Yunes JA; Centro Infantil Boldrini, Campinas, SP, Brazil; Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
  • Aparicio R; Laboratory of Structural Biology and Crystallography, Institute of Chemistry, University of Campinas, Campinas, SP, Brazil. Electronic address: aparicio@iqm.unicamp.br.
  • Murakami MT; Biosciences National Laboratory (LNBio), National Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil. Electronic address: mario.murakami@lnbio.cnpem.br.
Biochem Biophys Res Commun ; 474(4): 696-701, 2016 Jun 10.
Article en En | MEDLINE | ID: mdl-27154221
Plant aldo-keto reductases of the AKR4C subfamily play key roles during stress and are attractive targets for developing stress-tolerant crops. However, these AKR4Cs show little to no activity with previously-envisioned sugar substrates. We hypothesized a structural basis for the distinctive cofactor binding and substrate specificity of these plant enzymes. To test this, we solved the crystal structure of a novel AKR4C subfamily member, the AKR4C7 from maize, in the apo form and in complex with NADP(+). The binary complex revealed an intermediate state of cofactor binding that preceded closure of Loop B, and also indicated that conformational changes upon substrate binding are required to induce a catalytically-favorable conformation of the active-site pocket. Comparative structural analyses of homologues (AKR1B1, AKR4C8 and AKR4C9) showed that evolutionary redesign of plant AKR4Cs weakened interactions that stabilize the closed conformation of Loop B. This in turn decreased cofactor affinity and altered configuration of the substrate-binding site. We propose that these structural modifications contribute to impairment of sugar reductase activity in favor of other substrates in the plant AKR4C subgroup, and that catalysis involves a three-step process relevant to other AKRs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Plantas / Aldehído Reductasa / NADP Idioma: En Revista: Biochem Biophys Res Commun Año: 2016 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Plantas / Aldehído Reductasa / NADP Idioma: En Revista: Biochem Biophys Res Commun Año: 2016 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos