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Publication Abstract from PubMed

Herein, we present a novel esterase enzyme, Ade1, isolated from a metagenomic library of Amazonian dark earths soils, demonstrating its broad substrate promiscuity by hydrolyzing ester bonds linked to aliphatic groups. The three-dimensional structure of the enzyme was solved in the presence and absence of substrate (tributyrin), revealing its classification within the alpha/beta-hydrolase superfamily. Despite being a monomeric enzyme, enzymatic assays reveal a cooperative behavior with a sigmoidal profile (initial velocities vs substrate concentrations). Our investigation brings to light the allokairy/hysteresis behavior of Ade1, as evidenced by a transient burst profile during the hydrolysis of substrates such as p-nitrophenyl butyrate and p-nitrophenyl octanoate. Crystal structures of Ade1, coupled with molecular dynamics simulations, unveil the existence of multiple conformational structures within a single molecular state (E̅(1)). Notably, substrate binding induces a loop closure that traps the substrate in the catalytic site. Upon product release, the cap domain opens simultaneously with structural changes, transitioning the enzyme to a new molecular state (E̅(2)). This study advances our understanding of hysteresis/allokairy mechanisms, a temporal regulation that appears more pervasive than previously acknowledged and extends its presence to metabolic enzymes. These findings also hold potential implications for addressing human diseases associated with metabolic dysregulation.

Monomeric Esterase: Insights into Cooperative Behavior, Hysteresis/Allokairy.,Vinces TC, de Souza AS, Carvalho CF, Visnardi AB, Teixeira RD, Llontop EE, Bismara BAP, Vicente EJ, Pereira JO, de Souza RF, Yonamine M, Marana SR, Farah CS, Guzzo CR Biochemistry. 2024 May 7;63(9):1178-1193. doi: 10.1021/acs.biochem.3c00668. Epub , 2024 Apr 26. PMID:38669355^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.