Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.4
4.8
Journals
Biomolecules
Special Issues
Feature Papers in Enzymology—2nd Edition
share announcement

Feature Papers in Enzymology—2nd Edition

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Enzymology".

Deadline for manuscript submissions: closed (28 February 2025) | Viewed by 4119

Special Issue Editor

Prof. Dr. Piero Crespo

E-Mail Website
Guest Editor
CSIC Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Santander, Spain
Interests: Ras-ERK pathway spatial regulation; scaffold proteins; protein-protein interactions as therapeutic targets
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Based on the success of the first Special Issue, this second Special Issue of “Feature Papers in Enzymology” aims to collect high-quality research articles, review articles, and communications on all aspects of enzymology. It is dedicated to recent advances in the broad research area of enzymology and is inclusive of papers focused on the structure, function, and properties of enzymes, as well as catalytic and inhibition mechanisms of enzymes, mechanisms of drug action, and related advances in enzymes. This Special Issue will highlight advances in all types of enzymes, including hydrolases, oxidoreductases, lyases, transferases, ligases, and isomerases. Research related to cofactors (prosthetic groups, coenzymes, and metal ions) will also be of interest to this collection. It will be composed of a selection of exclusive papers from the Editorial Board Members (EBMs) of the Enzymology Section, as well as invited papers from relevant experts. We also welcome senior experts in the field to make contributions to this Special Issue. We aim to represent our section as an attractive open-access publishing platform for the enzymology research field.

Prof. Dr. Piero Crespo
Guest Editor

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. Biomolecules 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

  • structure and function
  • enzyme catalysis
  • enzyme inhibition
  • enzyme mechanisms
  • computational enzymology
  • biophysical characterization
  • structure determination
  • drug action
  • biochemical mechanisms
  • molecular forces
  • allosterism
  • orthosterism

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Related Special Issue

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

10 pages, 2607 KiB  
Article
Structural Plasticity of Flavin-Dependent Thymidylate Synthase Controlled by the Enzyme Redox State
by Ludovic Pecqueur, Murielle Lombard and Djemel Hamdane
Biomolecules 2025, 15(3), 318; https://doi.org/10.3390/biom15030318 - 21 Feb 2025
Viewed by 519
Abstract
2′-Deoxythymidine-5′-monophosphate, dTMP, is an essential precursor of thymine, one of the four canonical bases of DNA. In almost all living organisms, dTMP is synthesized de novo by a reductive methylation reaction of 2′-deoxyuridine-5′-monophosphate (dUMP) catalyzed by the thymidylate synthase, where the carbon used [...] Read more.
2′-Deoxythymidine-5′-monophosphate, dTMP, is an essential precursor of thymine, one of the four canonical bases of DNA. In almost all living organisms, dTMP is synthesized de novo by a reductive methylation reaction of 2′-deoxyuridine-5′-monophosphate (dUMP) catalyzed by the thymidylate synthase, where the carbon used for the methylation is derived from methylenetetrahydrofolate (CH2THF). Many microbes, including human pathogens, utilize the flavin-dependent thymidylate synthase encoded by the thyX gene to generate dTMP. The mechanism of action relies on the reduced coenzyme FADH−, which acts both as a mediator, facilitating methylene transfer from CH2THF to dUMP, and as a reducing agent. Here, we present for the first-time crystallographic structures of ThyX from Thermotoga maritima in the reduced state alone and in complex with dUMP. ThyX flavin reduction appears to order the active site, favoring a flavin conformation that drastically deviates from that observed in the oxidized enzyme. The structures show that FADH− potentially controls access to the folate site and the conformation of two active site loops, affecting the degree of accessibility of substrate pockets to the solvent. Our results provide the molecular basis for the sequential enzyme mechanism implemented by ThyX during dTMP biosynthesis. Full article
(This article belongs to the Special Issue Feature Papers in Enzymology—2nd Edition)
►▼ Show Figures

Graphical abstract

23 pages, 3261 KiB  
Article
The Diacylglycerol Acyltransferase 3 of Chlamydomonas reinhardtii Is a Disordered Protein Capable of Binding to Lipids Derived from Chloroplasts
by Natalia Pavia, Alberto Potenza, Felipe Hornos, José A. Poveda, Gabriela Gonorazky, José L. Neira, Ana M. Giudici and María Verónica Beligni
Biomolecules 2025, 15(2), 245; https://doi.org/10.3390/biom15020245 - 8 Feb 2025
Viewed by 871
Abstract
Understanding triacylglycerol (TAG) metabolism is crucial for developing algae as a source of biodiesel. TAGs are the main reservoir of energy in most eukaryotes. The final, rate-limiting step in the formation of TAGs is catalyzed by 1,2-diacylglycerol acyltransferases (DGATs). In the green alga [...] Read more.
Understanding triacylglycerol (TAG) metabolism is crucial for developing algae as a source of biodiesel. TAGs are the main reservoir of energy in most eukaryotes. The final, rate-limiting step in the formation of TAGs is catalyzed by 1,2-diacylglycerol acyltransferases (DGATs). In the green alga Chlamydomonas reinhardtii, DGAT3 is phylogenetically related to plant DGAT3 but unrelated to other DGATs from eukaryotes, such as DGAT1 and DGAT2. In this study, we described the conformational preferences and the lipid-binding features of the DGAT3 from C. reinhardtii. To characterize its conformational stability and structural features, we used several biophysical probes, namely, fluorescence, circular dichroism (CD), and differential scanning calorimetry (DSC). Our results showed that the protein was mainly disordered, containing a small population of folded conformations in a narrow pH range (pH 8 to 10). The conformational stability of the folded structure of DGAT3 was very low, as shown by urea or guanidinium denaturations. Thermal denaturation, followed by fluorescence or CD, as well as calorimetric denaturation, followed by DSC, did not yield any transition in the pH range where DGAT3 acquired a “native-like” conformation. Furthermore, we used two approaches to demonstrate the interaction of DGAT3 with lipid membranes at the pH at which it had acquired a “native-like” conformation. The first involved the measurement of anisotropy and fluorescence quenching of the protein. The second approach focused on examining possible modifications of the biophysical properties of lipids due to their interaction with DGAT3, through anisotropy measurements and leakage assays. Both methods produced consistent results, suggesting that DGAT3 preferentially interacted with negatively charged membranes. These results will allow the design of a more efficient and stable DGAT3, as well as an in-depth understanding of how the metabolism of TAGs is accomplished in C. reinhardtii. Full article
(This article belongs to the Special Issue Feature Papers in Enzymology—2nd Edition)
►▼ Show Figures

Graphical abstract

17 pages, 4441 KiB  
Article
Functional Characterization of the SHIP1-Domains Regarding Their Contribution to Inositol 5-Phosphatase Activity
by Spike Murphy Müller, Nina Nelson and Manfred Jücker
Biomolecules 2025, 15(1), 105; https://doi.org/10.3390/biom15010105 - 10 Jan 2025
Viewed by 1467
Abstract
The Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) is a multidomain protein consisting of two protein–protein interaction domains, the Src homology 2 (SH2) domain, and the proline-rich region (PRR), as well as three phosphoinositide-binding domains, the pleckstrin homology-like (PHL) domain, the 5-phosphatase [...] Read more.
The Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) is a multidomain protein consisting of two protein–protein interaction domains, the Src homology 2 (SH2) domain, and the proline-rich region (PRR), as well as three phosphoinositide-binding domains, the pleckstrin homology-like (PHL) domain, the 5-phosphatase (5PPase) domain, and the C2 domain. SHIP1 is commonly known for its involvement in the regulation of the PI3K/AKT signaling pathway by dephosphorylation of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) at the D5 position of the inositol ring. However, the functional role of each domain of SHIP1 for the regulation of its enzymatic activity is not well understood. To determine the contribution of the individual domains to catalytic activity, the full-length protein was compared with truncated constructs lacking one or more domain(s), regarding the substrate turnover (kcat) and catalytic efficiency (kcat/Km) towards ci8-PtdIns(3,4,5)P3. With this approach, it was possible to verify the allosteric activation of SHIP1 mediated by the C2 domain as described previously, while the PHL domain seemed instead to have a negative effect regarding catalytic efficiency. The full-length SHIP1 clearly displayed the highest turnover and the second-highest catalytic efficiency, showing the role of the SH2 domain and PRR not only in protein–protein interactions but also in catalysis. The SH2 domain increased substrate turnover but negatively affected catalytic efficiency. The linker between the SH2 and the PHL domains decreased the turnover number but positively influenced the catalytic efficiency. The PRR increased both the substrate turnover and the protein’s catalytic efficiency. The regression analysis of the Michaelis–Menten graph revealed SHIP1 to be an allosteric enzyme, with the PRR and the linker being the most involved domains in that regard. In summary, our data indicate a complex regulation of the enzymatic activity of SHIP1 by its individual domains. While the C2 domain and PRR at the carboxy-terminus have a positive effect on enzymatic activity, the SH2 and PHL domain at the amino-terminus inhibit catalytic efficiency. Full article
(This article belongs to the Special Issue Feature Papers in Enzymology—2nd Edition)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

33 pages, 7980 KiB  
Review
PERK-Olating Through Cancer: A Brew of Cellular Decisions
by Laurent Mazzolini and Christian Touriol
Biomolecules 2025, 15(2), 248; https://doi.org/10.3390/biom15020248 - 8 Feb 2025
Viewed by 947
Abstract
The type I protein kinase PERK is an endoplasmic reticulum (ER) transmembrane protein that plays a multifaceted role in cancer development and progression, influencing tumor growth, metastasis, and cellular stress responses. The activation of PERK represents one of the three signaling pathways induced [...] Read more.
The type I protein kinase PERK is an endoplasmic reticulum (ER) transmembrane protein that plays a multifaceted role in cancer development and progression, influencing tumor growth, metastasis, and cellular stress responses. The activation of PERK represents one of the three signaling pathways induced during the unfolded protein response (UPR), which is triggered, in particular, in tumor cells that constitutively experience various intracellular and extracellular stresses that impair protein folding within the ER. PERK activation can lead to both pro-survival and proapoptotic outcomes, depending on the cellular context and the extent of ER stress. It helps the reprogramming of the gene expression in cancer cells, thereby ensuring survival in the face of oncogenic stress, such as replicative stress and DNA damage, and also microenvironmental challenges, including hypoxia, angiogenesis, and metastasis. Consequently, PERK contributes to tumor initiation, transformation, adaptation to the microenvironment, and chemoresistance. However, sustained PERK activation in cells can also impair cell proliferation and promote apoptotic death by various interconnected processes, including mitochondrial dysfunction, translational inhibition, the accumulation of various cellular stresses, and the specific induction of multifunctional proapoptotic factors, such as CHOP. The dual role of PERK in promoting both tumor progression and suppression makes it a complex target for therapeutic interventions. A comprehensive understanding of the intricacies of PERK pathway activation and their impact is essential for the development of effective therapeutic strategies, particularly in diseases like cancer, where the ER stress response is deregulated in most, if not all, of the solid and liquid tumors. This article provides an overview of the knowledge acquired from the study of animal models of cancer and tumor cell lines cultured in vitro on PERK’s intracellular functions and their impact on cancer cells and their microenvironment, thus highlighting potential new therapeutic avenues that could target this protein. Full article
(This article belongs to the Special Issue Feature Papers in Enzymology—2nd Edition)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop