Structural Mechanism for the Temperature-Dependent Activation of the Hyperthermophilic Pf2001 Esterase

Nathalia Varejão, Rafael A. De-Andrade, Rodrigo V. Almeida, Cristiane D. Anobom, Debora Foguel, David Reverter

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13 Citations (Scopus)


© 2017 Elsevier Ltd Lipases and esterases constitute a group of enzymes that catalyze the hydrolysis or synthesis of ester bonds. A major biotechnological interest corresponds to thermophilic esterases, due to their intrinsic stability at high temperatures. The Pf2001 esterase from Pyrococcus furiosus reaches its optimal activity between 70°C and 80°C. The crystal structure of the Pf2001 esterase shows two different conformations: monomer and dimer. The structures reveal important rearrangements in the “cap” subdomain between monomer and dimer, by the formation of an extensive intertwined helical interface. Moreover, the dimer interface is essential for the formation of the hydrophobic channel for substrate selectivity, as confirmed by mutagenesis and kinetic analysis. We also provide evidence for dimer formation at high temperatures, a process that correlates with its enzymatic activation. Thus, we propose a temperature-dependent activation mechanism of the Pf2001 esterase via dimerization that is necessary for the substrate channel formation in the active-site cleft. Pf2001 is a hyperthermophilic esterase from P. furiosus that reaches its optimal activity at high temperatures. Varejão et al. provide structural insight into a temperature-dependent activation mechanism that converts Pf2001 into a stable and highly active dimer via the formation of a specific substrate channel in the active-site cleft.
Original languageEnglish
Pages (from-to)199-208.e3
Issue number2
Publication statusPublished - 6 Feb 2018


  • crystal structure
  • dimerization
  • esterase
  • lipase
  • temperature-dependent activation
  • thermophile


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