Enzymes最新文献_第4页

Sordaria macrospora carbonic anhydrases. 大孢子索达菌碳酸酐酶。

Enzymes Pub Date : 2025-01-01 Epub Date: 2025-07-08 DOI: 10.1016/bs.enz.2025.04.002

Niccolò Paoletti, Claudiu T Supuran, Clemente Capasso

{"title":"Sordaria macrospora carbonic anhydrases.","authors":"Niccolò Paoletti, Claudiu T Supuran, Clemente Capasso","doi":"10.1016/bs.enz.2025.04.002","DOIUrl":"https://doi.org/10.1016/bs.enz.2025.04.002","url":null,"abstract":"Sordaria macrospora, a coprophylous fungus used for the last three decades as a model organism for studying fruiting body development of fungi, encodes for four carbonic anhydrases (CAs, EC 4.2.1.1), CAS1-CAS4. CAS1-CAS3 are β-CAs and were investigated in detail in the last years, whereas CAS4, an α-class enzyme, was less investigated. All of them are crucial for the fungus, as the mutant lacking the genes encoding for these four enzymes showed a drastically reduced vegetative growth rate compared to the wild type organism. CAS4 is a secreted protein, CAS2 is mitochondrial, whereas CAS1 and CAS3 are cytosolic enzymes. The catalytic activity of CAS1-CAS3 for the CO2 hydration reaction showed that all of them possess a significant activity, with CAS3 being the most effective catalyst. The X-ray crystal structures of CAS1 and CAS2 were also obtained, showing that the two enzymes are tetramers (dimers of dimers) with an open active site in the case of CAS1 and a closed one for CAS2, similar to other plant/fungal/bacterial β-CAs studied so far. Detailed anion and sulfonamide inhibition studies were reported for all three β-Cas, which led to the identification of several effective inhibitors. Potential biotechnological applications of these enzymes for carbon (CO2) capture are also discussed.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"57 ","pages":"91-111"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252961","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}

引用次数: 0

Flaviviruses proteases. 黄病毒蛋白酶。

Enzymes Pub Date : 2025-01-01 Epub Date: 2025-09-27 DOI: 10.1016/bs.enz.2025.07.004

Lorenzo Zammarchi, Flavia Chechi, Michele Spinicci, Alessandro Bartoloni

引用次数: 0

Viral proteases as targets for antivirals drugs. 病毒蛋白酶作为抗病毒药物的靶点。

Enzymes Pub Date : 2025-01-01 Epub Date: 2025-10-22 DOI: 10.1016/bs.enz.2025.06.002

Luigi Pisano, Claudiu T Supuran

{"title":"Viral proteases as targets for antivirals drugs.","authors":"Luigi Pisano, Claudiu T Supuran","doi":"10.1016/bs.enz.2025.06.002","DOIUrl":"https://doi.org/10.1016/bs.enz.2025.06.002","url":null,"abstract":"The biochemical machinery of all viruses comprises enzymes able to cleave polyproteins formed after the transcription of the viral genetic material, which belong to the protease class. Viral proteases known so far belong to the aspartic, serine and cysteine protease classes, with no viral metalloprotease described to date. The tridimensional structure, biochemical properties and susceptibility to be inhibited by various classes of compounds for many such enzymes have been investigated in detail in the last decades. Many antiviral drugs target viral proteases which produce diseases in mammals, but such enzymes are also present in viruses which attack plants or bacteria, and potential applications for such enzymes or their inhibition started to be considered in recent years. The aspartic protease encoded in the HIV genome, the serine proteases found in various HCV serotypes and more recently the two cystein proteases from coronaviruses, including SARS CoV 2, are targeted by clinically used drugs belonging to the protease inhibitors, which effectively interrupt the life cycle of the virus, alone or in combination therapies with other antivirals and showed a relevant clinical success. Many other less investigated viruses encode for proteases belonging to the three classes mentioned above and they started to be investigated for obtaining novel antivirals for the management of Dengue, Zika, West Nile and other flaviviruses infections but also Chikungunya, Ebola, Marbug and various other filoviruses, for which few therapeutic options are available to date.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"58 ","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524683","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}

引用次数: 0

Hepatitis C virus (HCV) proteases: structure, function and inhibition strategies. 丙型肝炎病毒（HCV）蛋白酶：结构、功能和抑制策略

Enzymes Pub Date : 2025-01-01 Epub Date: 2025-08-06 DOI: 10.1016/bs.enz.2025.06.003

Pedro Henrique Oliveira Borges, Emmanuel Gras, Sabrina Baptista Ferreira, Floriano Paes Silva

{"title":"Hepatitis C virus (HCV) proteases: structure, function and inhibition strategies.","authors":"Pedro Henrique Oliveira Borges, Emmanuel Gras, Sabrina Baptista Ferreira, Floriano Paes Silva","doi":"10.1016/bs.enz.2025.06.003","DOIUrl":"https://doi.org/10.1016/bs.enz.2025.06.003","url":null,"abstract":"Hepatitis C virus (HCV) is a bloodborne, hepatotropic RNA virus and a serious global health burden, infecting over 50 million people worldwide, with the majority residing in low- and middle-income countries (LMICs), that significantly contributes to chronic liver diseases like cirrhosis and hepatocellular carcinoma. While no vaccines are available for HCV yet, over the years the success of direct-acting antivirals (DAAs) has been contributing with improved cure rates among treatment-naïve and treatment-experienced patients. However, many challenges remain due to undiagnosed infections and limited access to DAAs in LMICs. Thus, understanding of the molecular biology of HCV is pivotal in driving therapeutic advances, particularly the characterization of its two major proteases: the NS2/3 protease, a cysteine protease responsible for the first cleavage event of the polyprotein; and the NS3/4A protease, a serine protease that cleaves the remainder of the HCV genome. These proteases have been extensively studied as drug targets, although there is still much to learn. The NS3/4A protease has been a validated target for the development of DAAs, with several FDA-approved drugs in recent years. Yet, many challenges remain, as the genetic diversity of HCV has been leading to the emergence of drug-resistant strains that require the administration of the costly pan-genotypic DAAs. In this chapter we explore the structure and functions of NS2/3 and NS3/4A in the viral life cycle, how DAAs engage such targets and which mutations drive resistance. We conclude by discussing future and even less explored approaches in hopes of contributing to the current HCV drug development scenario.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"58 ","pages":"151-182"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524693","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}

引用次数: 0

Challenges for developing selective viral protease inhibitors as antiinfectives. 开发选择性病毒蛋白酶抑制剂作为抗感染药物的挑战。

Enzymes Pub Date : 2025-01-01 Epub Date: 2025-07-16 DOI: 10.1016/bs.enz.2025.06.009

Claudiu T Supuran, Luigi Pisano

{"title":"Challenges for developing selective viral protease inhibitors as antiinfectives.","authors":"Claudiu T Supuran, Luigi Pisano","doi":"10.1016/bs.enz.2025.06.009","DOIUrl":"https://doi.org/10.1016/bs.enz.2025.06.009","url":null,"abstract":"The biochemical machinery of most viruses comprises proteases which are crucial for their life cycle. In the last decades, proteases from pathogenic viruses started to be considered as potential drug targets, and this led to the development of several classes of effective antivirals used for the management of HIV, HCV and SARS CoV 2 infections. More than 25 clinically used protease inhibitors (PIs) are now available for the management of these three infections, but many other viruses encode for proteases which started to be considered only recently as potential drug targets. They include enterovirises, filoviruses such as Zika, Dengue and West Nile viruses, Chikungunya and other togaviruses, Ebola, Marbug and many other hemorrhagic viruses. The proteases of many such pathogens have been cloned, characterized and in some cases also crystallized in complex with inhibitors, but no compounds progressed yet to clinical trials. There are several relevant challenges in designing PIs as novel antivirals, such as: (i) the drug design strategies of peptidomimetic inhibitors, which are many times complex and expensive; (ii) the difficulties in identifying non-peptidomimetic PIs; (iii) the selectivity for the target versus host proteases of the identified PIs; (iv) their metabolism, absorption and in vivo antiviral activity, and, most importantly, (v) the emergence of drug/multidrug resistance due to the high mutation rates of many viruses. Many of these challenges started to be approached by innovative strategies which will be duscussed in the chapter.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"58 ","pages":"319-335"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524553","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}

引用次数: 0

Fungal α-carbonic anhydrases. 真菌α-碳酸酐酶。

Enzymes Pub Date : 2025-01-01 Epub Date: 2025-07-19 DOI: 10.1016/bs.enz.2025.07.003

Katia D'Ambrosio, Anna Di Fiore, Vincenzo Alterio, Martina Buonanno, Vincenzo Massimiliano Vivenzio, Simona Maria Monti, Giuseppina De Simone, Emma Langella

引用次数: 0

Coronaviruses main proteases and their inhibitors. 冠状病毒主要是蛋白酶及其抑制剂。

Enzymes Pub Date : 2025-01-01 Epub Date: 2025-09-27 DOI: 10.1016/bs.enz.2025.07.005

Claudiu T Supuran, Clemente Capasso

{"title":"Coronaviruses main proteases and their inhibitors.","authors":"Claudiu T Supuran, Clemente Capasso","doi":"10.1016/bs.enz.2025.07.005","DOIUrl":"https://doi.org/10.1016/bs.enz.2025.07.005","url":null,"abstract":"The SARS-CoV-2 main protease (Mpro) plays a pivotal role in the viral life cycle by cleaving polyproteins pp1a and pp1ab into functional non-structural proteins (NSPs), including components essential for RNA replication, such as nsp7, nsp8, and RNA-dependent RNA polymerase. The high sequence conservation across coronaviruses and absence of closely related human proteases make Mpro an attractive target for selective antiviral interventions. Recent efforts in drug discovery have led to the development of a wide spectrum of Mpro inhibitors, including covalent peptidomimetics (e.g., nirmatrelvir) and non-covalent small molecules with enhanced pharmacological profiles, such as ensitrelvir. Structure-based drug design, fragment-based drug discovery (FBDD), high-throughput screening (HTS), and in silico approaches have contributed to identification of novel scaffolds and optimization of binding interactions within the catalytic pocket. Non-covalent inhibitors offer reversible binding mechanisms that reduce off-target effects and are particularly promising for clinical translation. However, challenges such as the limited oral bioavailability of peptidomimetic compounds, metabolic instability, and emerging resistance highlight the need for further optimization. Ongoing research is exploring prodrug strategies, advanced delivery systems, and combinatorial regimens that integrate Mpro inhibitors with other antivirals to achieve synergistic effects and suppress resistance. This chapter provides a comprehensive overview of the current landscape of Mpro-targeted therapeutics and emphasizes their potential role in future pandemic preparedness.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"58 ","pages":"183-208"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524612","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}

引用次数: 0

Malassezia spp. carbonic anhydrases. 马拉色菌属碳酸酐酶。

Enzymes Pub Date : 2025-01-01 Epub Date: 2025-07-16 DOI: 10.1016/bs.enz.2025.04.001

Silvia Selleri, Andrea Angeli

{"title":"Malassezia spp. carbonic anhydrases.","authors":"Silvia Selleri, Andrea Angeli","doi":"10.1016/bs.enz.2025.04.001","DOIUrl":"10.1016/bs.enz.2025.04.001","url":null,"abstract":"Carbonic anhydrases (CAs) are essential metalloenzymes that catalyse the reversible conversion of CO₂ to bicarbonate, playing a crucial role in pH regulation, CO₂ sensing, and metabolic homeostasis. In Malassezia species, β-class CAs have emerged as promising drug targets for antifungal and dermatological applications, particularly in conditions such as dandruff and seborrheic dermatitis. Among the studied Malassezia species, the carbonic anhydrases from M. globosa (MgCA), M. restricta (MreCA) and M. pachydermatis (MpaCA) have been extensively characterized, demonstrating significant functional differences in both inhibition and activation mechanisms. This chapter explores the inhibition of Malassezia CAs using diverse classes of inhibitors, including sulfonamides, boronic acids, phenols, dithiocarbamates, and benzoxaboroles. Many of these compounds exhibit selective inhibition of fungal CAs over human isoforms, underscoring their potential as novel antifungal agents. Additionally, activation studies have revealed that both MgCA and MreCA can be modulated by biogenic amines and amino acids, with MreCA displaying markedly higher sensitivity, particularly to catecholamines like L-adrenaline, suggesting a potential link between stress responses and fungal virulence. The differential inhibition and activation profiles of Malassezia β-CAs provide valuable insights into fungal physiology, enzyme regulation, and potential therapeutic interventions. These findings establish a strong foundation for the rational design of selective inhibitors and activators that could serve as next-generation antifungal agents.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"57 ","pages":"65-89"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252026","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}

引用次数: 0

Coronaviruses papain-like proteases and their inhibitors. 冠状病毒木瓜蛋白酶及其抑制剂。

Enzymes Pub Date : 2025-01-01 Epub Date: 2025-10-13 DOI: 10.1016/bs.enz.2025.06.006

Ahmed E Elsawi, Haytham O Tawfik, Wagdy M Eldehna

{"title":"Coronaviruses papain-like proteases and their inhibitors.","authors":"Ahmed E Elsawi, Haytham O Tawfik, Wagdy M Eldehna","doi":"10.1016/bs.enz.2025.06.006","DOIUrl":"https://doi.org/10.1016/bs.enz.2025.06.006","url":null,"abstract":"The multipurpose enzyme papain-like protease (PLpro) is crucial for both immune evasion and viral multiplication. The replication-transcription complex is formed when PLpro, encoded by nonstructural protein 3 (nsp3), cleaves the viral polyprotein to release nsp1 through nsp4. Furthermore, by eliminating ubiquitin and ISG15 from key immune signaling proteins, such as IRF3, STING, and MDA5, PLpro impairs host antiviral defenses by reducing type I interferon responses. The catalytic triad and several functional domains, including the flexible BL2 loop that regulates access to the viral polyprotein substrate and inhibitor, as well as the SUb1 and SUb2 binding sites for ISG15/Ub recognition, are structural features of PLpro. Due to these features, PLpro is a desirable target for both allosteric and active-site inhibition. Numerous prospective inhibitors have been identified through drug repurposing and natural product screening, supported by structural and computational analyses that highlight key interaction sites. The biological significance, structural intricacy, and therapeutic potential of PLpro as a dual-action antiviral target, which can inhibit viral replication and restore host immune function, are highlighted in this chapter.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"58 ","pages":"209-249"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524628","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}

引用次数: 0

Bacteriophage endolysins. Bacteriophage endolysins。

Enzymes Pub Date : 2025-01-01 Epub Date: 2025-09-27 DOI: 10.1016/bs.enz.2025.06.008

Nidhi Prajapati, Dharmendra Prajapati, Anil Patani, Sherzodbek Tashbaev, Gulomov Gafurjon Shavkatbek Ugli, Ashish Patel

引用次数: 0