| Full text | |
| Author(s): Show less - |
Vinces, Tania Churasacari
;
de Souza, Anacleto Silva
;
Carvalho, Cecilia F.
;
Visnardi, Aline Biazola
;
Teixeira, Raphael D.
;
Llontop, Edgar E.
;
Bismara, Beatriz Aparecida Passos
;
Vicente, Elisabete J.
;
Pereira, Jose O.
;
de Souza, Robson Francisco
;
Yonamine, Mauricio
;
Marana, Sandro Roberto
;
Farah, Chuck Shaker
;
Guzzo, Cristiane R.
Total Authors: 14
|
| Document type: | Journal article |
| Source: | BIOCHEMISTRY; v. 63, n. 9, p. 16-pg., 2024-04-26. |
| Abstract | |
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 (E-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 (E-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. (AU) | |
| FAPESP's process: | 21/10577-0 - Biology of Bacteria and Bacteriophages Research Center |
| Grantee: | Shaker Chuck Farah |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 19/12234-2 - Isolation and structural studies on the Xanthomonas citri Type IV pilus and T4SS pilus |
| Grantee: | Edgar Enrique Llontop Cornejo |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 22/08730-7 - Protein structural biology applied in the study of c-di-GMP signaling and bacterial secretion systems |
| Grantee: | Cristiane Rodrigues Guzzo Carvalho |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 21/05262-0 - Study of c-di-GMP signaling involving LIC_11920 in Leptospira interrogans |
| Grantee: | Aline Biazola Visnardi |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 19/00195-2 - Understanding the c-di-GMP signaling networks and the Type II secretion system present into the human pathogen Leptospira interrogans Copenhageni |
| Grantee: | Cristiane Rodrigues Guzzo Carvalho |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 17/17303-7 - Structure and function of bacterial secretion systems |
| Grantee: | Shaker Chuck Farah |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 20/04680-0 - Design of different fragments of SARS-CoV-2 surface protein spike for the development of fast diagnostic test and vaccine |
| Grantee: | Cristiane Rodrigues Guzzo Carvalho |
| Support Opportunities: | Regular Research Grants |