Catalytic Reaction Mechanics of Enzymatic Reactions

A special issue of Catalysts (ISSN 2073-4344). This special issue belongs to the section "Biocatalysis".

Deadline for manuscript submissions: closed (10 April 2022) | Viewed by 3429

Special Issue Editors

Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130012, China
Interests: the relationship between enzyme structure and function; computer-aided drug design; computational structural biology; machine learning
Special Issues, Collections and Topics in MDPI journals
Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China
Interests: computational structural biology; protein interaction network; machine learning
School of Information Science and Technology, Northeast Normal University, Changchun 130117, China
Interests: computational chemistry; artificial intelligence; deep learning; chemical databases; quantum chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Theoretical methods (molecular docking, molecular dynamics simulation, quantum mechanical/molecular mechanics, and so on) are a new cross-biological means with the development of biological science and computer science technology. They have been applied to the research of biological macromolecular catalytic mechanism, protein conformation change between enzyme and ligand, which can affect the catalytic efficiency of the enzyme, and rational design of enzyme. Hence, in order to better explore the catalytic reaction mechanism of many macromolecules, it is necessary to introduce relevant research into the Special Issue to promote the development of this field. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: structure–activity relationship between protein and ligand, QM/MM enzyme catalytic reaction mechanism, structural modification of enzymes, and rational design of enzymes.

We look forward to receiving your contributions.

Prof. Dr. Weiwei Han
Prof. Dr. Minghui Li
Prof. Dr. Lihong Hu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Catalysts is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • rational design of enzymes
  • computational catalysis
  • molecular dynamics simulations
  • QM/MM

Published Papers (2 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

20 pages, 3198 KiB  
Article
Studies on the Selectivity Mechanism of Wild-Type E. coli Thioesterase ‘TesA and Its Mutants for Medium- and Long-Chain Acyl Substrates
by Xinyue Zhang, Hao Zhang, Shanshan Guan, Zhijian Luo, Jingwen E, Zhijie Yang, Juan Du and Song Wang
Catalysts 2022, 12(9), 1026; https://0-doi-org.brum.beds.ac.uk/10.3390/catal12091026 - 09 Sep 2022
Cited by 1 | Viewed by 1340
Abstract
E. coli thioesterase ‘TesA is an important enzyme in fatty acid production. Medium-chain fatty acids (MCFAs, C6-C10) are of great interest due to their similar physicochemical properties to petroleum-based oleo-chemicals. It has been shown that wild-type ‘TesA had better selectivity for long-chain acyl [...] Read more.
E. coli thioesterase ‘TesA is an important enzyme in fatty acid production. Medium-chain fatty acids (MCFAs, C6-C10) are of great interest due to their similar physicochemical properties to petroleum-based oleo-chemicals. It has been shown that wild-type ‘TesA had better selectivity for long-chain acyl substrates (≥C16), while the two mutants ‘TesAE142D/Y145G and ‘TesAM141L/E142D/Y145G had better selectivity for medium-chain acyl substrates. However, it is difficult to obtain the selectivity mechanism of substrates for proteins by traditional experimental methods. In this study, in order to obtain more MCFAs, we analyzed the binding mode of proteins (‘TesA, ‘TesAE142D/Y145G and ‘TesAM141L/E142D/Y145G) and substrates (C16/C8-N-acetylcysteamine analogs, C16/C8-SNAC), the key residues and catalytic mechanisms through molecular docking, molecular dynamics simulations and the molecular mechanics Poisson–Boltzmann surface area (MM/PBSA). The results showed that several main residues related to catalysis, including Ser10, Asn73 and His157, had a strong hydrogen bond interaction with the substrates. The mutant region (Met141-Tyr146) and loop107–113 were mainly dominated by Van der Waals contributions to the substrates. For C16-SNAC, except for ‘TesAM141L/E142D/Y145G with large conformational changes, there were strong interactions at both head and tail ends that distorted the substrate into a more favorable high-energy conformation for the catalytic reaction. For C8-SNAC, the head and tail found it difficult to bind to the enzyme at the same time due to insufficient chain length, which made the substrate binding sites more variable, so ‘TesAM141L/E142D/Y145G with better binding sites had the strongest activity, and ‘TesA had the weakest activity, conversely. In short, the matching substrate chain and binding pocket length are the key factors affecting selectivity. This will be helpful for the further improvement of thioesterases. Full article
(This article belongs to the Special Issue Catalytic Reaction Mechanics of Enzymatic Reactions)
Show Figures

Figure 1

15 pages, 5727 KiB  
Article
Exploration of the Interactions between Maltase–Glucoamylase and Its Potential Peptide Inhibitors by Molecular Dynamics Simulation
by Shanshan Guan, Xu Han, Zhan Li, Xifei Xu, Yongran Cui, Zhiwen Chen, Shuming Zhang, Shi Chen, Yaming Shan, Song Wang and Hao Li
Catalysts 2022, 12(5), 522; https://0-doi-org.brum.beds.ac.uk/10.3390/catal12050522 - 07 May 2022
Cited by 1 | Viewed by 1607
Abstract
Diabetes mellitus, a chronic metabolic disorder, represents a serious threat to human health. The gut enzyme maltase–glucoamylase (MGAM) has attracted considerable attention as a potential therapeutic target for the treatment of type 2 diabetes. Thus, developing novel inhibitors of MGAM holds the promise [...] Read more.
Diabetes mellitus, a chronic metabolic disorder, represents a serious threat to human health. The gut enzyme maltase–glucoamylase (MGAM) has attracted considerable attention as a potential therapeutic target for the treatment of type 2 diabetes. Thus, developing novel inhibitors of MGAM holds the promise of improving clinical management. The dipeptides, Thr-Trp (TW) and Trp-Ala (WA), are known inhibitors of MGAM; however, studies on how they interact with MGAM are lacking. The work presented here explored these interactions by utilizing molecular docking and molecular dynamics simulations. Results indicate that the active center of the MGAM could easily accommodate the flexible peptides. Interactions involving hydrogen bonds, cation-π, and hydrophobic interactions are predicted between TW/WA and residues including Tyr1251, Trp1355, Asp1420, Met1421, Glu1423, and Arg1510 within MGAM. The electrostatic energy was recognized as playing a dominant role in both TW-MGAM and WA-MGAM systems. The binding locations of TW/WA are close to the possible acid-base catalytic residue Asp1526 and might be the reason for MGAM inhibition. These findings provide a theoretical structural model for the development of future inhibitors. Full article
(This article belongs to the Special Issue Catalytic Reaction Mechanics of Enzymatic Reactions)
Show Figures

Figure 1

Back to TopTop