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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 21620

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Prof. Dr. Piotr Paneth

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1. International Centre for Research on Innovative Biobased Materials (ICRI-BioM)—International Research Agenda, Lodz University of Technology, Lodz, Poland
2. Faculty of Chemistry, Institute of Applied Radiation Chemistry, Lodz University of Technology, Lodz, Poland
Interests: isotope effects; mechanism of chemical and enzymatic reactions; enzyme inhibition; isotopic fractionation; isotope-ratio mass spectrometry; computational chemistry; docking
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Regional Project aims to collect high-quality research articles, review articles, and communications on all aspects of biochemistry from Poland. We encourage the submission of manuscripts that provide novel and mechanistic insights and papers that report significant advances in the fields.

The areas of interest for the regional collection include but are not limited to topics such as:

Cellular function and structure;
Cell signaling;
Cell Metabolism;
Proteostasis and Disease;
Protein biosynthesis;
Gene and protein structure and expression;
Cancer pathology and biology;
Aging biology and age-related diseases;
Drugs and pharmaceutics;
Post-translational modifications in Health and Disease;
New approaches in the management of hypoxic tumors;
Cancer metabolism and molecular genetics;
Enzymology and structural biology;
Metalloenzymes;
Enzyme activation and inhibition;
Targeting human enzymes involved in tumorigenesis;
Function and structure of lipid membrane;
Drug distribution in the body;
Protein interactions and functional nucleic acids;
Epigenetic and genetic regulatory mechanisms;
Lipid metabolism;
Drug resistance;
Role of intestinal microbes in diseases and human health;
Characterization and development of small molecules for targeting metabolic pathways essential for the life cycle of human pathogens;
Neurochemistry;
Glycobiology;
Immunology;
Stem cell biology;
Regenerative therapy;
Membrane Channels and Transporters;
Membrane Receptors.

Prof. Dr. Piotr Paneth
Collection Editor

Manuscript Submission Information

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Published Papers (10 papers)

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Research

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15 pages, 2692 KiB

Open AccessArticle

A Standardized Protocol for Assuring the Validity of Proteomics Results from Liquid Chromatography–High-Resolution Mass Spectrometry

by Andrzej Gawor and Ewa Bulska

Int. J. Mol. Sci. 2023, 24(7), 6129; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076129 - 24 Mar 2023

Viewed by 2390

Abstract

Significant advances in the technological development of mass spectrometry in the field of proteomics and the generation of extremely large amounts of data require a very critical approach to assure the validity of results. Commonly used procedures involved liquid chromatography followed by high-resolution mass spectrometry measurements. Proteomics analysis is used in many fields including the investigation of the metabolism of biologically active substances in organisms. Thus, there is a need to care about the validity of the obtained results. In this work, we proposed a standardized protocol for proteomic analysis using liquid chromatography–high-resolution mass spectrometry, which covers all of these analytical steps to ensure the validity of the results. For this purpose, we explored the requirements of the ISO/IEC 17025:2017 standard as a reference document for quality control in biochemistry research-based mass spectrometry. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Poland)

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15 pages, 4501 KiB

Open AccessArticle

TZD-Based Hybrid Molecules Act as Dual Anti-Mycobacterium tuberculosis and Anti-Toxoplasma gondii Agents

by Katarzyna Dzitko, Barbara Kaproń, Agata Paneth, Adrian Bekier, Tomasz Plech, Piotr Paneth and Nazar Trotsko

Int. J. Mol. Sci. 2023, 24(3), 2069; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032069 - 20 Jan 2023

Cited by 1 | Viewed by 1885

Abstract

Two distinct intracellular pathogens, namely Mycobacterium tuberculosis (Mtb) and Toxoplasma gondii (Tg), cause major public health problems worldwide. In addition, serious and challenging health problems of co-infections of Tg with Mtb have been recorded, especially in developing countries. Due to this fact, as well as the frequent cases of resistance to the current drugs, novel anti-infectious therapeutics, especially those with dual (anti-Tg and anti-Mtb) modes of action, are needed. To address this issue, we explored the anti-Tg potential of thiazolidinedione-based (TZD-based) hybrid molecules with proven anti-Mtb potency. Several TZD hybrids with pyridine-4-carbohydrazone (PCH) or thiosemicarbazone (TSC) structural scaffolds were more effective and more selective than sulfadiazine (SDZ) and trimethoprim (TRI). Furthermore, all of these molecules were more selective than pyrimethamine (PYR). Further studies for the most potent TZD-TSC hybrids 7, 8 and 10 and TZD-PCH hybrid molecule 2 proved that these compounds are non-cytotoxic, non-genotoxic and non-hemolytic. Moreover, they could cross the blood–brain barrier (BBB), which is a critical factor linked with ideal anti-Tg drug development. Finally, since a possible link between Tg infection and the risk of glioblastoma has recently been reported, the cytotoxic potential of TZD hybrids against human glioblastoma cells was also evaluated. TZD-PCH hybrid molecule 2 was found to be the most effective, with an IC₅₀ of 19.36 ± 1.13 µg/mL against T98G cells. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Poland)

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15 pages, 2201 KiB

Open AccessArticle

1,2-Hydrogenation and Transhydrogenation Catalyzed by 3-Ketosteroid Δ¹-Dehydrogenase from Sterolibacterium denitrificans—Kinetics, Isotope Labelling and QM:MM Modelling Studies

by Agnieszka M. Wojtkiewicz, Michał Glanowski, Piotr Waligórski, Tomasz Janeczko and Maciej Szaleniec

Int. J. Mol. Sci. 2022, 23(23), 14660; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314660 - 24 Nov 2022

Cited by 1 | Viewed by 1397

Abstract

Bacteria and fungi that are able to metabolize steroids express 3-ketosteroid-Δ¹-dehydrogenases (KstDs). KstDs such as AcmB form Sterolibacterium denitrificans Chol-1 catalyze the enantioselective 1α,2β-dehydrogenation of steroids to their desaturated analogues, e.g., the formation of 1,4-androstadiene-3,17-dione (ADD) from 4-androsten-3,17-dione (AD). The reaction catalyzed by KstD can be reversed if the appropriate electron donor, such as benzyl viologen radical cation, is present. Furthermore, KstDs can also catalyze transhydrogenation, which is the transfer of H atoms between 3-ketosteroids and 1-dehydrosteroids. In this paper, we showed that AcmB exhibits lower pH optima for hydrogenation and dehydrogenation by 3.5–4 pH units than those observed for KstD from Nocardia corallina. We confirmed the enantiospecificity of 1α,2β-hydrogenation and 1α,2β-transhydrogenation catalyzed by AcmB and showed that, under acidic pH conditions, deuterons are introduced not only at 2β but also at the 1α position. We observed a higher degree of H/D exchange at Y363, which activates the C2-H bond, compared to that at FAD, which is responsible for redox at the C1 position. Furthermore, for the first time, we observed the introduction of the third deuteron into the steroid core. This effect was explained through a combination of LC-MS experiments and QM:MM modelling, and we attribute it to a decrease in the enantioselectivity of C2-H activation upon the deuteration of the 2β position. The increase in the activation barrier resulting from isotopic substitution increases the chance of the formation of d³-substituted 3-ketosteroids. Finally, we demonstrate a method for the synthesis of 3-ketosteroids chirally deuterated at 1α,2β positions, obtaining 1α,2β-d²-4-androsten-3,17-dione with a 51% yield (8.61 mg). Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Poland)

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15 pages, 3362 KiB

Open AccessArticle

Biological Activity of fac-[Re(CO)₃(phen)(aspirin)], fac-[Re(CO)₃(phen)(indomethacin)] and Their Original Counterparts against Ishikawa and HEC-1A Endometrial Cancer Cells

by Olga Kuźmycz, Aleksandra Kowalczyk and Paweł Stączek

Int. J. Mol. Sci. 2022, 23(19), 11568; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911568 - 30 Sep 2022

Viewed by 1423

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are inhibitors of cyclooxygenase enzyme (COX) and were found to have positive effects in reducing the risk of developing gynecological cancers. However, long-term administration of NSAIDs carries the risk of various side effects, including those in the digestive and circulatory systems. Therefore, there is a constant need to develop new NSAID derivatives. In this work, we investigated rhenium NSAIDs, comparing their effects on endometrial cancer cells with original NSAIDs, demonstrating the high activity of aspirin and indomethacin derivatives. The cytotoxic activity of rhenium derivatives against the Ishikawa and HEC-1A cancer cell lines was higher than that of the original NSAIDs. The IC₅₀ after 24-h incubation of Ishikawa and HEC-1A were 188.06 µM and 394.06 µM for rhenium aspirin and 228.6 µM and 1459.3 µM for rhenium indomethacin, respectively. At the same time, IC₅₀ of aspirin and indomethacin were 10,024.42 µM and 3295.3 µM for Ishikawa, and 27,255.8 µM and 5489.3 µM for HEC-1A, respectively. Moreover, these derivatives were found to inhibit the proliferation of both cell lines in a time- and state-dependent manner. The Ishikawa cell proliferation was strongly inhibited by rhenium aspirin and rhenium indomethacin after 72-h incubation (*** = p < 0.001), while the HEC-1A proliferation was inhibited by the same agents already after 24-h incubation (*** = p < 0.001). Furthermore, the ROS level in the mitochondria of the tested cells generated in the presence of rhenium derivatives was higher than the original NSAIDs. That was associated with rhenium indomethacin exclusively, which had a significant effect (*** = p < 0.001) on both Ishikawa and HEC-1A cancer cells. Rhenium aspirin had a significant effect (*** = p < 0.001) on the mitochondrial ROS level of Ishikawa cells only. Overall, the research revealed a high potential of the rhenium derivatives of aspirin and indomethacin against endometrial cancer cells compared with the original NSAIDs. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Poland)

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12 pages, 12784 KiB

Open AccessArticle

The Role of Bradykinin Receptors in Hereditary Angioedema Due to C1-Inhibitor Deficiency

by Wojciech Dyga, Aleksander Obtulowicz, Tomasz Mikolajczyk, Anna Bogdali, Pawel Dubiela and Krystyna Obtulowicz

Int. J. Mol. Sci. 2022, 23(18), 10332; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810332 - 07 Sep 2022

Cited by 1 | Viewed by 1257

Abstract

Background: Hereditary angioedema (HAE) is a rare, genetic disease caused by the decreased level or function of the C1 inhibitor. The primary mediator of symptoms in HAE is bradykinin acting through its two receptors, namely receptors 1 (BR1) and 2 (BR2). Although BR2 is well characterized, the role of BR1 remains unclear. Objective: To study the role of bradykinin receptors 1 (BR1) in the etiopathogenesis of HAE. Methods: A total of 70 individuals, 40 patients with HAE, and 30 healthy subjects were recruited to the study. HAE was diagnosed in accordance with the international guideline. The level of bradykinin receptors was determined in populations of CD3⁺, CD4⁺, CD8⁺, and CD14⁺⁺CD16⁻, CD14⁺⁺CD16⁺ monocytes. In addition, the level of disease activity-specific markers was measured. Results: There were statistically significant differences in the subpopulation of lymphocytes and monocytes between patients with HAE compared to healthy subjects. The level of BR1 and BR2 on PBMCs was comparable in healthy subjects and HAE patients during remission with significant overexpression of both receptors, triggered by HAE attack. Moreover, a significant increase in TNF-alpha and IL-1 plasma levels was observed among HAE patients. Conclusions: BR1 expression may play an important role in the pathomechanism of HAE. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Poland)

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12 pages, 4386 KiB

Open AccessArticle

Influence of Association on Binding of Disaccharides to YKL-39 and hHyal-1 Enzymes

by Agnieszka Krzemińska, José-Emilio Sánchez-Aparicio, Jean-Didier Maréchal, Agata Paneth and Piotr Paneth

Int. J. Mol. Sci. 2022, 23(14), 7705; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23147705 - 12 Jul 2022

Viewed by 1805

Abstract

Disaccharide complexes have been shown experimentally to be useful for drug delivery or as an antifouling surface biofilm, and are promising drug-encapsulation and delivery candidates. Although such complexes are intended for medical applications, to date no studies at the molecular level have been devoted to the influence of complexation on the enzymatic decomposition of polysaccharides. A theoretical approach to this problem has been hampered by the lack of a suitable computational tool for binding such non-covalent complexes to enzymes. Herein, we combine quantum-mechanical calculations of disaccharides complexes with a nonstandard docking GaudiMM engine that can perform such a task. Our results on four different complexes show that they are mostly stabilized by electrostatic interactions and hydrogen bonds. This strong non-covalent stabilization demonstrates the studied complexes are some excellent candidates for self-assembly smart materials, useful for drug encapsulation and delivery. Their advantage lies also in their biocompatible and biodegradable character. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Poland)

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23 pages, 4251 KiB

Open AccessArticle

The Val34Met, Thr164Ile and Ser220Cys Polymorphisms of the β2-Adrenergic Receptor and Their Consequences on the Receptor Conformational Features: A Molecular Dynamics Simulation Study

by Aneta Archala, Wojciech Plazinski and Anita Plazinska

Int. J. Mol. Sci. 2022, 23(10), 5449; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105449 - 13 May 2022

Viewed by 1341

Abstract

The gene encoding the β2-adrenergic receptor (β2-AR) is polymorphic, which results in possible differences in a primary structure of this protein. It has been shown that certain types of polymorphisms are correlated with some clinical features of asthma, including airways reactivity, whereas the influence of other is not yet understood. Among polymorphisms affecting amino acids at positions 16, 27, 34, 164 and 220, the latter three are present in the crystal structure of β2-AR, which facilitates studying them by means of molecular dynamics simulations. The current study was focused on investigating to what extent the three polymorphisms of β2-AR (i.e., Val34Met, Thr164Ile and Ser220Cys) affect the interaction of β2-AR with its natural molecular environment which includes: lipid bilayer (in the case of all three polymorphs) and Gs protein (which participates in β2-AR-mediated signaling; in the case of Ser220Cys). We have designed and carried out a series of molecular dynamics simulations at different level of resolution (i.e., either coarse-grained or atomistic simulations), accompanied by thermodynamic integration protocol, in order to identify potential polymorphism-induced alterations in structural, conformational or energetic features of β2-AR. The results indicate the lack of significant differences in the case of energies involved in the β2-AR-lipid bilayer interactions. Some differences have been observed when considering the polymorphism-induced alterations in β2-AR-Gs protein binding, but their magnitude is also negligible in relation to the absolute free energy difference correlated with the β2-AR-Gs affinity. The Val34Met and Thr164Ile polymorphisms are weakly correlated with alteration of the conformational features of the receptor around polymorphic sites. On the contrary, it has been concluded that the Ser220Cys polymorphism is correlated with several structural alterations located in the intracellular region of β2-AR, which can induce G-protein binding and, subsequently, the polymorphism-correlated therapeutic responses. More precisely, these alterations involve vicinity of intracellular loops and, in part, are the direct consequence of disturbed interactions of Ser/Cys220 sidechain within 5th transmembrane domain. Structurally, the dynamic structure exhibited by the β2-AR^Ser220 polymorph is closer to the Gs-compatible structure of β2-AR. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Poland)

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15 pages, 4208 KiB

Open AccessArticle

Theoretical Studies of Cyanophycin Dipeptides as Inhibitors of Tyrosinases

by Agnieszka Krzemińska, Natalia Kwiatos, Franciela Arenhart Soares and Alexander Steinbüchel

Int. J. Mol. Sci. 2022, 23(6), 3335; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063335 - 19 Mar 2022

Cited by 3 | Viewed by 2610

Abstract

The three-dimensional structure of tyrosinase has been crystallized from many species but not from Homo sapiens. Tyrosinase is a key enzyme in melanin biosynthesis, being an important target for melanoma and skin-whitening cosmetics. Several studies employed the structure of tyrosinase from Agaricus bisporus as a model enzyme. Recently, 98% of human genome proteins were elucidated by AlphaFold. Herein, the AlphaFold structure of human tyrosinase and the previous model were compared. Moreover, tyrosinase-related proteins 1 and 2 were included, along with inhibition studies employing kojic and cinnamic acids. Peptides are widely studied for their inhibitory activity of skin-related enzymes. Cyanophycin is an amino acid polymer produced by cyanobacteria and is built of aspartic acid and arginine; arginine can be also replaced by other amino acids. A new set of cyanophycin-derived dipeptides was evaluated as potential inhibitors. Aspartate–glutamate showed the strongest interaction and was chosen as a leading compound for future studies. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Poland)

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Review

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30 pages, 891 KiB

Open AccessReview

Delivery of Nucleotide Sugars to the Mammalian Golgi: A Very Well (un)Explained Story

by Dorota Maszczak-Seneczko, Maciej Wiktor, Edyta Skurska, Wojciech Wiertelak and Mariusz Olczak

Int. J. Mol. Sci. 2022, 23(15), 8648; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158648 - 03 Aug 2022

Cited by 4 | Viewed by 2971

Abstract

Nucleotide sugars (NSs) serve as substrates for glycosylation reactions. The majority of these compounds are synthesized in the cytoplasm, whereas glycosylation occurs in the endoplasmic reticulum (ER) and Golgi lumens, where catalytic domains of glycosyltransferases (GTs) are located. Therefore, translocation of NS across the organelle membranes is a prerequisite. This process is thought to be mediated by a group of multi-transmembrane proteins from the SLC35 family, i.e., nucleotide sugar transporters (NSTs). Despite many years of research, some uncertainties/inconsistencies related with the mechanisms of NS transport and the substrate specificities of NSTs remain. Here we present a comprehensive review of the NS import into the mammalian Golgi, which consists of three major parts. In the first part, we provide a historical view of the experimental approaches used to study NS transport and evaluate the most important achievements. The second part summarizes various aspects of knowledge concerning NSTs, ranging from subcellular localization up to the pathologies related with their defective function. In the third part, we present the outcomes of our research performed using mammalian cell-based models and discuss its relevance in relation to the general context. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Poland)

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40 pages, 4142 KiB

Open AccessReview

Naturally-Sourced Antibacterial Polymeric Nanomaterials with Special Reference to Modified Polymer Variants

by Marian Rofeal, Fady Abdelmalek and Alexander Steinbüchel

Int. J. Mol. Sci. 2022, 23(8), 4101; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084101 - 07 Apr 2022

Cited by 19 | Viewed by 3336

Abstract

Despite the recent advancements in treating bacterial infections, antibiotic resistance (AR) is still an emerging issue. However, polymeric nanocarriers have offered unconventional solutions owing to their capability of exposing more functional groups, high encapsulation efficiency (EE) and having sustained delivery. Natural polymeric nanomaterials (NMs) are contemplated one of the most powerful strategies in drug delivery (DD) in terms of their safety, biodegradability with almost no side effects. Every nanostructure is tailored to enhance the system functionality. For example, cost-effective copper NPs could be generated in situ in cellulose sheets, demonstrating powerful antibacterial prospects for food safety sector. Dendrimers also have the capacity for peptide encapsulation, protecting them from proteolytic digestion for prolonged half life span. On the other hand, the demerits of naturally sourced polymers still stand against their capacities in DD. Hence, Post-synthetic modification of natural polymers could play a provital role in yielding new hybrids while retaining their biodegradability, which could be suitable for building novel super structures for DD platforms. This is the first review presenting the contribution of natural polymers in the fabrication of eight polymeric NMs including particulate nanodelivery and nanofabrics with antibacterial and antibiofilm prospects, referring to modified polymer derivatives to explore their full potential for obtaining sustainable DD products. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Poland)

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