EnzymesPub Date : 2024-01-01Epub Date: 2024-09-07DOI: 10.1016/bs.enz.2024.06.008
Alessandro Bonardi, Paola Gratteri
{"title":"Computational studies of tyrosinase inhibitors.","authors":"Alessandro Bonardi, Paola Gratteri","doi":"10.1016/bs.enz.2024.06.008","DOIUrl":"10.1016/bs.enz.2024.06.008","url":null,"abstract":"<p><p>Computational studies have significantly advanced the understanding of tyrosinase (TYR) function, mechanism, and inhibition, accelerating the development of more effective and selective inhibitors. This chapter provides an overview of in silico studies on TYR inhibitors, emphasizing key inhibitory chemotypes and the main residues involved in ligand-target interactions. The chapter discusses tools applied in the context of TYR inhibitor development, e.g., structure-based virtual screening, molecular docking, artificial intelligence, and machine learning algorithms.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"56 ","pages":"191-229"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2024-01-01Epub Date: 2024-06-01DOI: 10.1016/bs.enz.2024.05.004
Clemente Capasso, Claudiu T Supuran
{"title":"Overview on bacterial carbonic anhydrase genetic families.","authors":"Clemente Capasso, Claudiu T Supuran","doi":"10.1016/bs.enz.2024.05.004","DOIUrl":"https://doi.org/10.1016/bs.enz.2024.05.004","url":null,"abstract":"<p><p>Bacterial carbonic anhydrases (BCAs, EC 4.2.1.1) are indispensable enzymes in microbial physiology because they facilitate the hydration of carbon dioxide (CO<sub>2</sub>) to bicarbonate ions (HCO<sub>3</sub><sup>-</sup>) and protons (H<sup>+</sup>), which are crucial for various metabolic processes and cellular homeostasis. Their involvement spans from metabolic pathways, such as photosynthesis, respiration, to organic compounds production, which are pivotal for bacterial growth and survival. This chapter elucidates the diversity of BCA genetic families, categorized into four distinct classes (α, β, γ, and ι), which may reflect bacterial adaptation to environmental niches and their metabolic demands. The diversity of BCAs is essential not only for understanding their physiological roles but also for exploring their potential in biotechnology. Knowledge of their diversity enables researchers to develop innovative biocatalysts for industrial applications, including carbon capture technologies to convert CO<sub>2</sub> emissions into valuable products. Additionally, BCAs are relevant to biomedical research and drug development because of their involvement in bacterial pathogenesis and microbial survival within the host. Understanding the diversity and function of BCAs can aid in designing targeted therapeutics that interfere with bacterial metabolism and potentially reduce the risk of infections.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"55 ","pages":"1-29"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2024-01-01Epub Date: 2024-06-06DOI: 10.1016/bs.enz.2024.05.008
Molly S Youse, Katrina J Holly, Daniel P Flaherty
{"title":"Neisseria gonorrhoeae carbonic anhydrase inhibition.","authors":"Molly S Youse, Katrina J Holly, Daniel P Flaherty","doi":"10.1016/bs.enz.2024.05.008","DOIUrl":"https://doi.org/10.1016/bs.enz.2024.05.008","url":null,"abstract":"<p><p>Carbonic anhydrases (CAs) are ubiquitous enzymes that are found in all kingdoms of life. Though different classes of CAs vary in their roles and structures, their primary function is to catalyze the reaction between carbon dioxide and water to produce bicarbonate and a proton. Neisseria gonorrhoeae encodes for three distinct CAs (NgCAs) from three different families: an α-, a β-, and a γ-isoform. This chapter details the differences between the three NgCAs, summarizing their subcellular locations, roles, essentiality, structures, and enzyme kinetics. These bacterial enzymes have the potential to be drug targets; thus, previous studies have investigated the inhibition of NgCAs-primarily the α-isoform. Therefore, the classes of inhibitors that have been shown to bind to the NgCAs will be discussed as well. These classes include traditional CA inhibitors, such as sulfonamides, phenols, and coumarins, as well as non-traditional inhibitors including anions and thiocarbamates.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"55 ","pages":"243-281"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2024-01-01Epub Date: 2024-08-06DOI: 10.1016/bs.enz.2024.06.004
Luigi Franklin Di Costanzo
{"title":"Structural characterization of tyrosinases and an update on human enzymes.","authors":"Luigi Franklin Di Costanzo","doi":"10.1016/bs.enz.2024.06.004","DOIUrl":"10.1016/bs.enz.2024.06.004","url":null,"abstract":"<p><p>Tyrosinase, a pivotal enzyme in melanin biosynthesis, orchestrates the pigmentation process in humans, affecting skin, hair, and eye color. This chapter examines the three-dimensional structure and functional aspects of tyrosinases from various sources, highlighting their di-metal ion coordination crucial for catalytic activity. I explore the biochemical pathwayscheme catalyzed by tyrosinase, specifically the oxidation of L-tyrosine to L-dopaquinone, a precursor in melanin synthesis. Detailed structural analyses, including 3D structures obtained from X-ray crystallography and computational modeling, reveal key insights into the enzyme's active site, variations among tyrosinases, and substrate binding mechanisms. Furthermore, the chapter investigates the role of human tyrosinase variants, their inhibitors, essential for developing therapeutic and cosmetic applications targeting hyperpigmentation disorders. Structural characterizations of tyrosinase-inhibitor complexes provide a foundation for designing effective inhibitors, with compounds like kojic acid, L-mimosine, and (S)-3-amino-tyrosine demonstrating significant inhibitory potential. This comprehensive examination of the structure, function, and inhibition mechanisms of tyrosinase offers avenues for innovative treatments in biotechnology, health, and beyond.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"56 ","pages":"55-83"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2024-01-01Epub Date: 2024-09-07DOI: 10.1016/bs.enz.2024.05.010
Clemente Capasso, Claudiu T Supuran
{"title":"Overview on tyrosinases: Genetics, molecular biology, phylogenetic relationship.","authors":"Clemente Capasso, Claudiu T Supuran","doi":"10.1016/bs.enz.2024.05.010","DOIUrl":"10.1016/bs.enz.2024.05.010","url":null,"abstract":"<p><p>Tyrosinases (TYRs) are enzymes found in various organisms that are crucial for melanin biosynthesis, coloration, and UV protection. They play vital roles in insect cuticle sclerotization, mollusk shell formation, fungal and bacterial pigmentation, biofilm formation, and virulence. Structurally, TYRs feature copper-binding sites that are essential for catalytic activity, facilitating substrate oxidation via interactions with conserved histidine residues. TYRs exhibit diversity across animals, plants, fungi, mollusks, and bacteria, reflecting their roles and function. Eukaryotic TYRs undergo post-translational modifications, such as glycosylation, which affect protein folding and activity. Bacterial TYRs are categorized into five types based on their structural variation, domain organization and enzymatic properties, showing versatility across bacterial species. Moreover, bacterial TYRs, akin to fungal TYRs, have been implicated in the synthesis of secondary metabolites with antimicrobial properties. TYRs share significant sequence homology with hemocyanins, oxygen-carrier proteins in mollusks and arthropods, highlighting their evolutionary relationships. The evolution of TYRs underscores the dynamic nature of these enzymes and reflects adaptive strategies across diverse taxa.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"56 ","pages":"1-30"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2024-01-01Epub Date: 2024-06-01DOI: 10.1016/bs.enz.2024.05.003
Clemente Capasso, Claudiu T Supuran
{"title":"Bacterial ι-CAs.","authors":"Clemente Capasso, Claudiu T Supuran","doi":"10.1016/bs.enz.2024.05.003","DOIUrl":"https://doi.org/10.1016/bs.enz.2024.05.003","url":null,"abstract":"<p><p>Recent research has identified a novel class of carbonic anhydrases (CAs), designated ι-CA, predominantly found in marine diatoms, eukaryotic algae, cyanobacteria, bacteria, and archaea genomes. This class has garnered attention owing to its unique biochemical properties and evolutionary significance. Through bioinformatic analyses, LCIP63, a protein initially annotated with an unknown function, was identified as a potential ι-CA in the marine diatom Thalassiosira pseudonana. Subsequent biochemical characterization revealed that LCIP63 has CA activity and its preference for manganese ions over zinc, indicative of evolutionary adaptation to marine environments. Further exploration of bacterial ι-CAs, exemplified by Burkholderia territorii ι-CA (BteCAι), demonstrated catalytic efficiency and sensitivity to sulfonamide and inorganic anion inhibitors, the classical CA inhibitors (CAIs). The classification of ι-CAs into two variant types based on their sequences, distinguished by the COG4875 and COG4337 domains, marks a significant advancement in our understanding of these enzymes. Structural analyses of COG4337 ι-CAs from eukaryotic microalgae and cyanobacteria thereafter revealed a distinctive structural arrangement and a novel catalytic mechanism involving specific residues facilitating CO<sub>2</sub> hydration in the absence of metal ion cofactors, deviating from canonical CA behavior. These findings underscore the biochemical diversity within the ι-CA class and highlight its potential as a target for novel antimicrobial agents. Overall, the elucidation of ι-CA properties and mechanisms advances our knowledge of carbon metabolism in diverse organisms and underscores the complexity of CA evolution and function.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"55 ","pages":"121-142"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2024-01-01Epub Date: 2024-06-08DOI: 10.1016/bs.enz.2024.05.011
Katrina J Holly, Molly S Youse, Daniel P Flaherty
{"title":"Enterococci carbonic anhydrase inhibition.","authors":"Katrina J Holly, Molly S Youse, Daniel P Flaherty","doi":"10.1016/bs.enz.2024.05.011","DOIUrl":"https://doi.org/10.1016/bs.enz.2024.05.011","url":null,"abstract":"<p><p>Carbonic anhydrase metalloenzymes are encoded in genomes throughout all kingdoms of life with a conserved function catalyzing the reversible conversion of CO<sub>2</sub> to bicarbonate. Carbonic anhydrases have been well-investigated in humans, but are still relatively understudied in bacterial organisms, including Enterococci. Studies over the past decade have presented bacterial carbonic anhydrases as potential drug targets, with some chemical scaffolds potently inhibiting the Enterococcus carbonic anhydrases in vitro and displaying antimicrobial efficacy against Enterococcus organisms. While carbonic anhydrases in Enterococci still have much to be explored, hypotheses may be drawn from similar Gram-positive organisms for which known information exists about carbonic anhydrase function and relevance. Within this chapter is reported information and rational hypotheses regarding the subcellar locations, potential physiological roles, essentiality, structures, and kinetics of carbonic anhydrases in Enterococci.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"55 ","pages":"283-311"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2024-01-01Epub Date: 2024-07-26DOI: 10.1016/bs.enz.2024.07.001
Vincenzo Massimiliano Vivenzio, Davide Esposito, Simona Maria Monti, Giuseppina De Simone
{"title":"Bacterial α-CAs: a biochemical and structural overview.","authors":"Vincenzo Massimiliano Vivenzio, Davide Esposito, Simona Maria Monti, Giuseppina De Simone","doi":"10.1016/bs.enz.2024.07.001","DOIUrl":"https://doi.org/10.1016/bs.enz.2024.07.001","url":null,"abstract":"<p><p>Carbonic anhydrases belonging to the α-class are widely distributed in bacterial species. These enzymes have been isolated from bacteria with completely different characteristics including both Gram-negative and Gram-positive strains. α-CAs show a considerable similarity when comparing the biochemical, kinetic and structural features, with only small differences which reflect the diverse role these enzymes play in Nature. In this chapter, we provide a comprehensive overview on bacterial α-CA data, with a highlight to their potential biomedical and biotechnological applications.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"55 ","pages":"31-63"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2024-01-01Epub Date: 2024-08-23DOI: 10.1016/bs.enz.2024.05.002
Andrea Angeli
{"title":"Bacterial γ-carbonic anhydrases.","authors":"Andrea Angeli","doi":"10.1016/bs.enz.2024.05.002","DOIUrl":"https://doi.org/10.1016/bs.enz.2024.05.002","url":null,"abstract":"<p><p>Carbonic anhydrases (CAs) are a ubiquitous family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and protons, playing pivotal roles in a variety of biological processes including respiration, calcification, acid-base balance, and CO<sub>2</sub> fixation. Recent studies have expanded the understanding of CAs, particularly the γ-class from diverse biological sources such as pathogenic bacteria, extremophiles, and halophiles, revealing their unique structural adaptations and functional mechanisms that enable operation under extreme environmental conditions. This chapter discusses the comprehensive catalytic mechanism and structural insights from X-ray crystallography studies, highlighting the molecular adaptations that confer stability and activity to these enzymes in harsh environments. It also explores the modulation mechanism of these enzymes, detailing how different modulators interact with the active site of γ-CAs. Comparative analyzes with other CA classes elucidate the evolutionary trajectories and functional diversifications of these enzymes. The synthesis of this knowledge not only sheds light on the fundamental aspects of CA biology but also opens new avenues for therapeutic and industrial applications, particularly in designing targeted inhibitors for pathogenic bacteria and developing biocatalysts for industrial processes under extreme conditions. The continuous advancement in structural biology promises further insights into this enzyme family, potentially leading to novel applications in medical and environmental biotechnology.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"55 ","pages":"93-120"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2024-01-01Epub Date: 2024-07-05DOI: 10.1016/bs.enz.2024.06.006
Alessio Nocentini
{"title":"Sulfonamide inhibitors of bacterial carbonic anhydrases.","authors":"Alessio Nocentini","doi":"10.1016/bs.enz.2024.06.006","DOIUrl":"https://doi.org/10.1016/bs.enz.2024.06.006","url":null,"abstract":"<p><p>The increasing prevalence of antibiotic-resistant bacteria necessitates the exploration of novel therapeutic targets. Bacterial carbonic anhydrases (CAs) have been known for decades, but only in the past ten years they have garnered significant interest as drug targets to develop antibiotics having a diverse mechanism of action compared to the clinically used drugs. Significant progress has been made in the field in the past three years, with the validation in vivo of CAs from Neisseria gonorrhoeae, and vancomycin-resistant enterococci as antibiotic targets. This chapter compiles the state-of-the-art research on sulfonamide derivatives described as inhibitors of all known bacterial CAs. A section delves into the mechanisms of action of sulfonamide compounds with the CA classes identified in pathogenic bacteria, specifically α, β, and γ classes. Therefore, the inhibitory profiling of the bacterial CAs with classical and clinically used sulfonamide compounds is reported and analyzed. Another section covers various other series of sulfonamide CA inhibitors studied for the development of new antibiotics. By synthesizing current research findings, this chapter highlights the potential of sulfonamide inhibitors as a novel class of antibacterial agents and paves the way for future drug design strategies.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"55 ","pages":"143-191"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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