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Special Issue "Structure and Function of Metalloenzymes"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: 30 September 2020.

Special Issue Editor

Dr. Sérgio F. Sousa
Website
Guest Editor
UCIBIO/REQUIMTE, BioSIM - Departamento de BioMedicina,Faculdade de Medicina da Universidade do Porto, Porto, Portugal
Interests: computational enzymatic catalysis; QM/MM; docking; virtual screening; molecular dynamics simulations
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Metal ion cofactors play a fundamental role in many biologically enzymes contributing to the diversification of their associated chemistry, the strengthening of their catalytic role, and the modulation of their activity. In fact, metalloenzymes are very often among the most proficient catalysts in nature. For many of these systems, the presence of the metal atoms is directly involved in the catalytic activity displayed, while in others, the metal plays a structural role. Features like the identity of the metal atom and its oxidation and spin state often have a dramatic impact on the structure and activity of many metalloenzymes. However, some enzymes can accommodate without penalty different metal atoms.

The sheer impact that one single atom—metal—can have on the structure and activity of a biomolecule composed of several thousand non-metal atoms continues to impress scientists to this day, particularly as researchers worldwide continue to clarify, to the atomic level, the catalytic mechanisms of many metalloenzymes, using a variety of experimental and computational methodologies.

This Special Issue aims to gather original research papers, reviews, and communications focusing on the relation between metals, enzymes, and their structure and activity.

Dr. Sergio F. Sousa
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 papers will be 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. Molecules is an international peer-reviewed open access semimonthly 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 2000 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

  • biocatalysts
  • metals
  • coordination-sphere
  • active-site
  • transition state
  • metal stabilization
  • metal role

Published Papers (3 papers)

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Research

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Open AccessArticle
The Generation of the Oxidant Agent of a Mononuclear Nonheme Fe(II) Biomimetic Complex by Oxidative Decarboxylation. A DFT Investigation
Molecules 2020, 25(2), 328; https://doi.org/10.3390/molecules25020328 - 14 Jan 2020
Abstract
The oxidative decarboxylation of the iron(II) α-hydroxy acid (mandelic acid) complex model, biomimetic of Rieske dioxygenase, has been investigated at the density functional level. The explored mechanism sheds light on the role of the α-hydroxyl group on the dioxygen activation. The potential energy [...] Read more.
The oxidative decarboxylation of the iron(II) α-hydroxy acid (mandelic acid) complex model, biomimetic of Rieske dioxygenase, has been investigated at the density functional level. The explored mechanism sheds light on the role of the α-hydroxyl group on the dioxygen activation. The potential energy surfaces have been explored in different electronic spin states. The rate-determining step of the process is the proton transfer. The oxidative decarboxylation preferentially takes place on the quintet state. Full article
(This article belongs to the Special Issue Structure and Function of Metalloenzymes)
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Open AccessArticle
A Single-Turnover Kinetic Study of DNA Demethylation Catalyzed by Fe(II)/α-Ketoglutarate-Dependent Dioxygenase AlkB
Molecules 2019, 24(24), 4576; https://doi.org/10.3390/molecules24244576 - 13 Dec 2019
Cited by 1
Abstract
AlkB is a Fe(II)/α-ketoglutarate-dependent dioxygenase that repairs some alkylated bases of DNA and RNA in Escherichia coli. In the course of catalysis, oxidation of a co-substrate (α-ketoglutarate, αKG) leads to the formation of a highly reactive ‘oxyferryl’ enzyme-bound intermediate, Fe(IV) = O, [...] Read more.
AlkB is a Fe(II)/α-ketoglutarate-dependent dioxygenase that repairs some alkylated bases of DNA and RNA in Escherichia coli. In the course of catalysis, oxidation of a co-substrate (α-ketoglutarate, αKG) leads to the formation of a highly reactive ‘oxyferryl’ enzyme-bound intermediate, Fe(IV) = O, ensuring hydroxylation of the alkyl nucleobase adducts. Previous studies have revealed that AlkB is a flexible protein and can adopt different conformations during interactions with cofactors and DNA. To assess the conformational dynamics of the enzyme in complex with single- or double-stranded DNA in real-time mode, we employed the stopped-flow fluorescence method. N1-Methyladenine (m1A) introduced into a sequence of 15-mer oligonucleotides was chosen as the specific damage. Single-turnover kinetics were monitored by means of intrinsic fluorescence of the protein’s Trp residues, fluorescent base analogue 2-aminopurine (2aPu), and a dye–quencher pair (FAM/BHQ1). For all the fluorescent labels, the fluorescent traces showed several phases of consistent conformational changes, which were assigned to specific steps of the enzymatic process. These data offer an overall picture of the structural dynamics of AlkB and DNA during their interaction. Full article
(This article belongs to the Special Issue Structure and Function of Metalloenzymes)
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Review

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Open AccessReview
Molecular Imaging Probes Based on Matrix Metalloproteinase Inhibitors (MMPIs)
Molecules 2019, 24(16), 2982; https://doi.org/10.3390/molecules24162982 - 16 Aug 2019
Cited by 4
Abstract
Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent endopeptidases which are secreted or anchored in the cell membrane and are capable of degrading the multiple components of the extracellular matrix (ECM). MMPs are frequently overexpressed or highly activated in numerous human [...] Read more.
Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent endopeptidases which are secreted or anchored in the cell membrane and are capable of degrading the multiple components of the extracellular matrix (ECM). MMPs are frequently overexpressed or highly activated in numerous human diseases. Owing to the important role of MMPs in human diseases, many MMP inhibitors (MMPIs) have been developed as novel therapeutics, and some of them have entered clinical trials. However, so far, only one MMPI (doxycycline) has been approved by the FDA. Therefore, the evaluation of the activity of a specific subset of MMPs in human diseases using clinically relevant imaging techniques would be a powerful tool for the early diagnosis and assessment of the efficacy of therapy. In recent years, numerous MMPIs labeled imaging agents have emerged. This article begins by providing an overview of the MMP subfamily and its structure and function. The latest advances in the design of subtype selective MMPIs and their biological evaluation are then summarized. Subsequently, the potential use of MMPI-labeled diagnostic agents in clinical imaging techniques are discussed, including positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging (OI). Finally, this article concludes with future perspectives and clinical utility. Full article
(This article belongs to the Special Issue Structure and Function of Metalloenzymes)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Molecular Imaging Probes based on Matrix Metalloproteinase Inhibitors
Authors: Loganathan Rangasamy, Irene Ortín, Claire Coderch, Bruno Di Geronimo, Ana Ramos and Beatriz de Pascual-Teresa
Affiliation: Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925, Alcorcón, Madrid, Spain
Email: [email protected]
Abstract: Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent endopeptidases which are secreted or anchored in the cell membrane and are capable of degrading the multiple components of the extracellular matrix (ECM). MMPs are frequently overexpressed or highly activated in numerous human diseases, including cancer, atherosclerosis, stroke, arthritis, cardiovascular diseases, periodontal disease, respiratory tract disorders, glomerulonephritis, abdominal aortic aneurysm expansion, inflammatory bowel disease, neurodegeneration, chronic obstructive pulmonary disease, multiple sclerosis and liver fibrosis. Owing to the important role of MMPs in human diseases, many MMP inhibitors (MMPis) have been developed as novel therapeutics and some of them have entered clinical trials. However, none of them have successfully entered the market so far. The lack of selectivity toward specific MMP subtypes has been considered as the main factor responsible for this failure. Targeting of specific MMPs remains a challenge since most MMP subtypes share similar structure and function. Therefore, it is anticipated that the development of highly selective inhibitors for specific MMPs could solve the problem. On the other hand, evaluation of the activity of a specific subset of MMPs in human diseases using clinically relevant imaging techniques would be a powerful tool for the early diagnosis and assessment of the efficacy of therapy. In recent years, numerous MMPis labeled imaging agents have emerged. In this article, we begin providing an overview of the MMP subfamily and its structure and function. We then summarize the latest advances in the design of subtype selective MMP inhibitors and their biological evaluation. Subsequently, we discuss the potential use of MMPi-labeled diagnostic agents in clinical imaging techniques, including positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging (OI). Finally, we conclude with future perspectives and clinical utility.
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