Biomolecules & Therapeutics最新文献_第9页

Analysis of SARS-CoV-2 Mutations after Nirmatrelvir Treatment in a Lung Cancer Xenograft Mouse Model. 在肺癌异种移植小鼠模型中进行 Nirmatrelvir 治疗后的 SARS-CoV-2 变异分析

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-05 DOI: 10.4062/biomolther.2023.195

Bo Min Kang, Dongbum Kim, Jinsoo Kim, Kyeongbin Baek, Sangkyu Park, Ha-Eun Shin, Myeong-Heon Lee, Minyoung Kim, Suyeon Kim, Younghee Lee, Hyung-Joo Kwon

{"title":"Analysis of SARS-CoV-2 Mutations after Nirmatrelvir Treatment in a Lung Cancer Xenograft Mouse Model.","authors":"Bo Min Kang, Dongbum Kim, Jinsoo Kim, Kyeongbin Baek, Sangkyu Park, Ha-Eun Shin, Myeong-Heon Lee, Minyoung Kim, Suyeon Kim, Younghee Lee, Hyung-Joo Kwon","doi":"10.4062/biomolther.2023.195","DOIUrl":"10.4062/biomolther.2023.195","url":null,"abstract":"Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (Mpro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in Mpro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the Mpro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC50 values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"481-491"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elafibranor PPARα/δ Dual Agonist Ameliorates Ovalbumin-Induced Allergic Asthma. Elafibranor PPARα/δ 双激动剂可改善卵清蛋白诱发的过敏性哮喘

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-05 DOI: 10.4062/biomolther.2023.194

Ye-Eul Lee, Dong-Soon Im

{"title":"Elafibranor PPARα/δ Dual Agonist Ameliorates Ovalbumin-Induced Allergic Asthma.","authors":"Ye-Eul Lee, Dong-Soon Im","doi":"10.4062/biomolther.2023.194","DOIUrl":"10.4062/biomolther.2023.194","url":null,"abstract":"Asthma is characterized by chronic inflammation and respiratory tract remodeling. Peroxisome proliferator-activated receptors (PPARs) play important roles in the pathogenesis and regulation of chronic inflammatory processes in asthma. The role of PPARγ has been studied using synthetic PPARγ agonists in patients with asthma. However, involvement of PPARα/δ has not been studied in asthma. In the present study, we investigated if elafibranor, a PPARα/δ dual agonist, can modulate ovalbumin (OVA)-induced allergic asthma, which is a potential drug candidate for non-alcoholic fatty liver in obese patients. Elafibranor suppresses antigen-induced degranulation in RBL-2H3 mast cells without inducing cytotoxicity in vitro. In mice with OVA-induced allergic asthma, the administration of elafibranor suppressed OVA-induced airway hyper-responsiveness at a dose of 10 mg/kg. Elafibranor also suppressed the OVA-induced increase in immune cells and pro-inflammatory cytokine production in the bronchoalveolar lavage fluid (BALF). Histological studies suggested that elafibranor suppressed OVA-induced lung inflammation and mucin hyper-production in the bronchial airways. In addition, elafibranor suppressed OVA-induced increases in serum immunoglobulin E and IL-13 levels in BALF. Conversely, the present study suggests that elafibranor has the potential for use in patients with allergic asthma.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"460-466"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineered T Cell Receptor for Cancer Immunotherapy. 用于癌症免疫疗法的工程 T 细胞受体。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-07 DOI: 10.4062/biomolther.2023.197

So Won Lee, Hyang-Mi Lee

引用次数: 0

Selonsertib, an ASK1 Inhibitor, Ameliorates Ovalbumin-Induced Allergic Asthma during Challenge and Sensitization Periods. ASK1抑制剂Selonsertib能改善卵清蛋白诱发的过敏性哮喘的挑战期和致敏期症状。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-07 DOI: 10.4062/biomolther.2023.203

So-Young Han, Dong-Soon Im

{"title":"Selonsertib, an ASK1 Inhibitor, Ameliorates Ovalbumin-Induced Allergic Asthma during Challenge and Sensitization Periods.","authors":"So-Young Han, Dong-Soon Im","doi":"10.4062/biomolther.2023.203","DOIUrl":"10.4062/biomolther.2023.203","url":null,"abstract":"Apoptosis signal-regulating kinase 1 (ASK1) is an upstream signaling molecule in oxidative stress-induced responses. Because oxidative stress is involved in asthma pathogenesis, ASK1 gene deficiency was investigated in animal models of allergic asthma. However, there is no study to investigate whether ASK1 inhibitors could be applied for asthma to date. Selonsertib, a potent and selective ASK1 inhibitor, was applied to BALB/c mice of an ovalbumin (OVA)-induced allergic asthma model. Selonsertib suppressed antigen-induced degranulation of RBL-2H3 mast cells in a concentration-dependent manner. The administration of selonsertib both before OVA sensitization and OVA challenge significantly reduced airway hyperresponsiveness, and suppressed eosinophil numbers and inflammatory cytokine levels in the bronchoalveolar lavage fluid. Histopathologic examination elucidated less inflammatory responses and reduced mucin-producing cells around the peribronchial regions of the lungs. Selonsertib also suppressed the IgE levels in serum and the protein levels of IL-13 in the bronchoalveolar lavage fluid. These results suggest that selonsertib may ameliorate allergic asthma by suppressing immune responses and be applicable to allergic asthma.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"451-459"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gut Microbiota Metabolite Messengers in Brain Function and Pathology at a View of Cell Type-Based Receptor and Enzyme Reaction. 从基于细胞类型的受体和酶反应看肠道微生物群代谢物信使在大脑功能和病理学中的作用

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.4062/biomolther.2024.009

Bada Lee, Soo Min Lee, Jae Won Song, Jin Woo Choi

{"title":"Gut Microbiota Metabolite Messengers in Brain Function and Pathology at a View of Cell Type-Based Receptor and Enzyme Reaction.","authors":"Bada Lee, Soo Min Lee, Jae Won Song, Jin Woo Choi","doi":"10.4062/biomolther.2024.009","DOIUrl":"10.4062/biomolther.2024.009","url":null,"abstract":"The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"403-423"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibitory Action of 1,3,5-Trihydroxybenzene on UVB-Induced NADPH Oxidase 4 through AMPK and JNK Signaling Pathways. 1,3,5-三羟基苯通过 AMPK 和 JNK 信号通路对紫外线诱导的 NADPH 氧化酶 4 起抑制作用

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-25 DOI: 10.4062/biomolther.2024.054

Chaemoon Lim, Mei Jing Piao, Kyoung Ah Kang, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Dae Whan Kim, Joo Mi Yi, Yung Hyun Choi, Jin Won Hyun

{"title":"Inhibitory Action of 1,3,5-Trihydroxybenzene on UVB-Induced NADPH Oxidase 4 through AMPK and JNK Signaling Pathways.","authors":"Chaemoon Lim, Mei Jing Piao, Kyoung Ah Kang, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Dae Whan Kim, Joo Mi Yi, Yung Hyun Choi, Jin Won Hyun","doi":"10.4062/biomolther.2024.054","DOIUrl":"10.4062/biomolther.2024.054","url":null,"abstract":"Specific sensitivity of the skin to ultraviolet B (UVB) rays is one of the mechanisms responsible for widespread skin damage. This study tested whether 1,3,5-trihydroxybenzene (THB), a compound abundant in marine products, might inhibit UVB radiation-induced NADPH oxidase 4 (NOX4) in both human HaCaT keratinocytes and mouse dorsal skin and explore its cytoprotective mechanism. The mechanism of action was determined using western blotting, immunocytochemistry, NADP+/NADPH assay, reactive oxygen species (ROS) detection, and cell viability assay. THB attenuated UVB-induced NOX4 expression both in vitro and in vivo, and suppressed UVB-induced ROS generation via NADP+ production, resulting in increased cell viability with decreased apoptosis. THB also reduced the expression of UVB-induced phosphorylated AMP-activated protein kinase (AMPK) and phosphorylated c-Jun N-terminal kinase (JNK). THB suppressed UVB-induced NOX4 expression and ROS generation by inhibiting AMPK and JNK signaling pathways, thereby inhibiting cellular damage. These results showed that THB could be developed as a UV protectant.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 4","pages":"499-507"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-Inflammatory Activities of (+)-Afzelechin against Lipopolysaccharide-Induced Inflammation. (+)-Afzelechin 对脂多糖诱发炎症的抗炎活性

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-07 DOI: 10.4062/biomolther.2023.204

In-Chul Lee, Jong-Sup Bae

{"title":"Anti-Inflammatory Activities of (+)-Afzelechin against Lipopolysaccharide-Induced Inflammation.","authors":"In-Chul Lee, Jong-Sup Bae","doi":"10.4062/biomolther.2023.204","DOIUrl":"10.4062/biomolther.2023.204","url":null,"abstract":"In this study, we investigated the potential protective effects of (+)-afzelechin (AZC), a natural compound that is derived from Bergenia ligulata, on lipopolysaccharide (LPS)-induced inflammatory responses. AZC is known to have antioxidant, anticancer, antimicrobial, and cardiovascular protective properties. However, knowledge regarding the therapeutic potential of AZC against LPS-induced inflammatory responses is limited. Thus, we investigated the protective attributes of AZC against inflammatory damage caused by LPS exposure. We examined the effects of AZC on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). In addition, the effects of AZC on the expression of iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were analyzed in the lung tissues of LPS-injected mice. Data revealed that AZC promoted the production of HO-1, inhibited the interaction between luciferase and nuclear factor (NF)-κB, and reduced the levels of COX-2/PGE2 and iNOS/NO, thereby leading to a decrease in the signal transducer and activator of transcription (STAT)-1 phosphorylation. Moreover, AZC facilitated the nuclear translocation of Nrf2, increased the binding activity between Nrf2 and the antioxidant response elements (AREs), and lowered the expression of IL-1β in the LPS-treated HUVECs. In the animal model, AZC significantly reduced the expression of iNOS in the lung tissue structure and the TNF-α level in the bronchoalveolar lavage fluid. These findings demonstrate that AZC possesses anti-inflammatory properties that regulate iNOS through the inhibition of both NF-κB expression and p-STAT-1. Consequently, AZC has potential as a future candidate for the development of new clinical substances for the treatment of pathological inflammation.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"467-473"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure-Activity Relationship and Functional Evaluation of Cannabinoid Type-1 Receptor. 大麻素 1 型受体的结构-活性关系和功能评估。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-07 DOI: 10.4062/biomolther.2023.205

Shujie Wang, Xinru Tian, Suresh Paudel, Sungho Ghil, Choon-Gon Jang, Kyeong-Man Kim

{"title":"Structure-Activity Relationship and Functional Evaluation of Cannabinoid Type-1 Receptor.","authors":"Shujie Wang, Xinru Tian, Suresh Paudel, Sungho Ghil, Choon-Gon Jang, Kyeong-Man Kim","doi":"10.4062/biomolther.2023.205","DOIUrl":"10.4062/biomolther.2023.205","url":null,"abstract":"The type-1 cannabinoid receptor (CB1R) is a potential therapeutic target in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Owing to their structural diversity, it is not easy to derive general structure-activity relationships (SARs) for CB1R ligands. In this study, CB1R ligands were classified into six structural families, and the corresponding SAR was determined for their affinities for CB1R. In addition, we determined their functional activities for the activation of extracellular signal-regulated kinases (ERKs). Among derivatives of indol-3-yl-methanone, the highest ligand affinity was observed when a pentyl and a naphthalenyl group were attached to the N1 position of the indole ring and the carbon site of the methanone moiety, respectively. In the case of adamantane indazole-3-carboxamide derivatives, the presence of fluorine in the pentyl group, the substituent at the N1 position of the indazole ring, strongly increased the affinity for CB1R. For (naphthalen-1-yl) methanone derivatives, the presence of 4-alkoxynaphthalene in the methanone moiety was more beneficial for the affinity to CB1R than that of a heterocyclic ring. The functional activities of the tested compounds, evaluated through ERK assay, were correlated with their affinity for CB1R, suggesting their agonistic nature. In conclusion, this study provides valuable insight for designing novel ligands for CB1R, which can be used to control psychiatric disorders and drug abuse.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"442-450"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular Vesicles Derived from Adipose Stem Cells Alleviate Systemic Sclerosis by Inhibiting TGF-β Pathway. 脂肪干细胞衍生的细胞外小泡通过抑制 TGF-β 通路缓解系统性硬化症

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-05 DOI: 10.4062/biomolther.2023.191

Eunae Kim, Hark Kyun Kim, Jae Hoon Sul, Jeongmi Lee, Seung Hyun Baek, Yoonsuk Cho, Jihoon Han, Junsik Kim, Sunyoung Park, Jae Hyung Park, Yong Woo Cho, Dong-Gyu Jo

{"title":"Extracellular Vesicles Derived from Adipose Stem Cells Alleviate Systemic Sclerosis by Inhibiting TGF-β Pathway.","authors":"Eunae Kim, Hark Kyun Kim, Jae Hoon Sul, Jeongmi Lee, Seung Hyun Baek, Yoonsuk Cho, Jihoon Han, Junsik Kim, Sunyoung Park, Jae Hyung Park, Yong Woo Cho, Dong-Gyu Jo","doi":"10.4062/biomolther.2023.191","DOIUrl":"10.4062/biomolther.2023.191","url":null,"abstract":"Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"432-441"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural Insights into the Interaction of Terpenoids with Streptomyces avermitilis CYP107P2. 萜类化合物与 Streptomyces avermitilis CYP107P2 相互作用的结构见解。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-05 DOI: 10.4062/biomolther.2024.045

Eunseo Jeong, Vitchan Kim, Changmin Kim, Yoo-Bin Lee, Donghak Kim

{"title":"Structural Insights into the Interaction of Terpenoids with Streptomyces avermitilis CYP107P2.","authors":"Eunseo Jeong, Vitchan Kim, Changmin Kim, Yoo-Bin Lee, Donghak Kim","doi":"10.4062/biomolther.2024.045","DOIUrl":"10.4062/biomolther.2024.045","url":null,"abstract":"Streptomyces avermitilis genome includes 33 genes encoding monooxygenation-catalyzing cytochrome P450 enzymes. We investigated the structure of CYP107P2 and its interactions with terpenoid compounds. The recombinant CYP107P2 protein was expressed in Escherichia coli and the purified enzyme exhibited a typical P450 spectrum upon CO-binding in its reduced state. Type-I substrate-binding spectral titrations were observed with various terpenoid compounds, including α-pinene, β-pinene, α-terpinyl acetate, and (+)-3-carene. The calculated binding affinities (Kd) ranged from 15.9 to 50.8 μM. The X-ray crystal structure of CYP107P2 was determined at 1.99 Å resolution, with a well-conserved overall P450 folding conformation. The terpenoid compound docking models illustrated that the structural interaction between monoterpenes and CYP107P2, with the distance between heme and terpenes ranging from 3.4 to 5.4 Å, indicates potential substrate binding for P450 enzyme. This study suggests that CYP107P2 is a Streptomyces P450 enzyme capable of catalyzing terpenes as substrates, signifying noteworthy advancements in comprehending a novel P450 enzyme's involvement in terpene reactions.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"474-480"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0