Biochemistry Biochemistry最新文献

Iron-Sulfur Cluster Enzymes of the Methylerythritol Phosphate Pathway: IspG and IspH. 甲基赤藓糖醇磷酸途径的铁硫簇酶：IspG和IspH。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-17 Epub Date: 2025-05-27 DOI: 10.1021/acs.biochem.4c00714

Andrew Douw, Jordi Perez-Gil, Gerhard Schenk, Claudia E Vickers

{"title":"Iron-Sulfur Cluster Enzymes of the Methylerythritol Phosphate Pathway: IspG and IspH.","authors":"Andrew Douw, Jordi Perez-Gil, Gerhard Schenk, Claudia E Vickers","doi":"10.1021/acs.biochem.4c00714","DOIUrl":"10.1021/acs.biochem.4c00714","url":null,"abstract":"Iron-sulfur cluster (Fe-S) enzymes catalyze important biological processes in cellular metabolism. They evolved in the preoxic world and are oxygen sensitive; biology has therefore evolved a range of mechanisms to protect them from oxidative damage. The 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis has two Fe-S enzymes: IspG and IspH. Both enzymes utilize 3:1 site-differentiated [4Fe-4S] clusters to perform rather unique dehydroxylation reactions. They may play roles in facilitating oxidative stress sensing and signaling. While bacterial IspG and IspH are well characterized, plant IspG and IspH are not. A particularly fascinating aspect of these enzymes is their ability to balance both their biosynthetic catalytic roles and their presumptive signaling roles in metabolism. Here we review current knowledge about the mechanism, structures, and function of IspG and IspH, and we propose future research directions to help answer the many remaining questions about them. We also provide a primer for investigators keen to start working with these enzymes, as they share with the Fe-S family a set of unique handling and experimental challenges.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"2544-2555"},"PeriodicalIF":2.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural and Functional Investigation of Putative Peptidase from Mycolicibacterium phlei: An Exclusive Endopeptidase among S9C Subfamily. 细菌性分枝杆菌肽酶的结构和功能研究：一种S9C亚家族独有的内肽酶。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-17 Epub Date: 2025-05-28 DOI: 10.1021/acs.biochem.5c00047

Khileshwari Chandravanshi, Sahayog N Jamdar, Rahul Singh, Ashwani Kumar, Alok Mahato, Richa Agrawal, Sanjukta A Kumar, Amit Kumar, Ravindra D Makde

{"title":"Structural and Functional Investigation of Putative Peptidase from Mycolicibacterium phlei: An Exclusive Endopeptidase among S9C Subfamily.","authors":"Khileshwari Chandravanshi, Sahayog N Jamdar, Rahul Singh, Ashwani Kumar, Alok Mahato, Richa Agrawal, Sanjukta A Kumar, Amit Kumar, Ravindra D Makde","doi":"10.1021/acs.biochem.5c00047","DOIUrl":"10.1021/acs.biochem.5c00047","url":null,"abstract":"Peptidases of the prolyl oligopeptidase (S9 MEROPS) family play a pivotal role in various physiological processes. Among the S9 family, the S9C subfamily is remarkably diverse in exhibiting enzymatic activities such as acylaminoacyl peptidase, dipeptidyl peptidase, endopeptidase, and carboxypeptidase activity. Predicting enzymatic activity for putative peptidase of the S9C subfamily remains a significant challenge. Here, we report the biophysical and biochemical characterization of a putative peptidase from Mycolicibacterium phlei (S9mp; UniProt: A0A5N5URA7) from the S9C subfamily. Our findings establish S9mp as the first known member of this family to predominantly exhibit endopeptidase activity, which requires a peptide substrate with a free C-terminal for efficient binding and catalysis. Arg443 was identified as a critical residue for substrate binding and stabilization, particularly for smaller peptide substrates. Arg443Ala mutagenesis leads to a several-fold reduction in the enzymatic activity, underscoring its crucial role. Structural analyses using SAXS and AlphaFold confirmed a tetrameric assembly featuring a central oligomeric pore, which may influence substrate accessibility and limit the cleavage of peptides up to nine amino acids in length. These findings deepen our understanding of S9mp's enzymatic mechanisms and provide valuable insights into the molecular basis of its substrate specificity.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"2596-2610"},"PeriodicalIF":2.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Geranylated Natural Product Simamycin Disrupts the Allosteric Catalysis of tRNA-2-selenouridine Synthase SelU. 香叶酰化天然产物西霉素破坏trna -2-硒尿嘧啶合成酶SelU的变构催化作用。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-17 Epub Date: 2025-05-25 DOI: 10.1021/acs.biochem.5c00053

Stephen J Dansereau, Alexander Shekhtman, Francesco Epifano, Salvatore Genovese, Serena Fiorito, Thomas J Begley, Jia Sheng

{"title":"A Geranylated Natural Product Simamycin Disrupts the Allosteric Catalysis of tRNA-2-selenouridine Synthase SelU.","authors":"Stephen J Dansereau, Alexander Shekhtman, Francesco Epifano, Salvatore Genovese, Serena Fiorito, Thomas J Begley, Jia Sheng","doi":"10.1021/acs.biochem.5c00053","DOIUrl":"10.1021/acs.biochem.5c00053","url":null,"abstract":"tRNA-2-selenouridine synthase (SelU) is a tRNA-modifying enzyme that is instrumental to bacterial translation by exploiting certain chalcogens. Specifically, this enzyme catalyzes the geranylation of 2-thiouridine at the wobble position of three bacterial tRNAs to enhance the recognition of codons ending in guanosine over adenosine using geranyl pyrophosphate as the cofactor. In addition, SelU is also the working enzyme for a selenation process at the same tRNA position in the presence of selenophosphate. How this enzyme conducts two mechanistically different reactions is a fundamentally interesting question. In order to gain more details about the substrate recognition of SelU, in this work, we identified a small natural compound simamycin (5'-O-geranyluridine) with strong interactions with this enzyme. Further, through biophysical affinity assays and NMR structural studies, we postulated an allosteric mechanism of SelU catalysis involving cooperativity among each domain and a conformational rearrangement around the active site of its N-terminal domain. This conclusion is supported by the bimolecular quenching constants, number of binding sites, and thermodynamic parameters calculated for this compound complexed with the N-terminal domain of SelU.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"2640-2648"},"PeriodicalIF":2.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Fascinating Intricacy of pSer/Thr-Specific Phosphatases and Their Higher-Order Complexes: Emerging Concepts. pSer/ thr特异性磷酸酶及其高阶复合物的迷人复杂性：新兴概念。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-17 Epub Date: 2025-06-05 DOI: 10.1021/acs.biochem.5c00183

Laura Scheinost, Maja Köhn

引用次数: 0

Drug Delivery: Built by Biochemistry. 药物传递：由生物化学构建。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-17 DOI: 10.1021/acs.biochem.5c00275

Alanna Schepartz

引用次数: 0

Correction to "Identifying Allosteric Hotspots in Mycobacterium tuberculosis cAMP Receptor Protein through Structural Homology". 更正“通过结构同源性鉴定结核分枝杆菌cAMP受体蛋白变构热点”。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-17 Epub Date: 2025-06-05 DOI: 10.1021/acs.biochem.5c00102

Stephen P Dokas, Daniel K Taylor, Lydia L Good, Sanuja Mohanaraj, Anna Park, Rodrigo A Maillard

引用次数: 0

Structural Insights into Lipoate Ligase A-Mediated Antibody Modifications. 脂酸连接酶a介导的抗体修饰的结构见解。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-17 Epub Date: 2025-03-20 DOI: 10.1021/acs.biochem.5c00040

Kazutoshi Takahashi, Shunsuke Yamazaki, Yutaka Matsuda

引用次数: 0

In Vivo Ribosome-Amplified MetaBOlism, RAMBO, Effect Observed by Real Time Pulse Chase, RTPC, NMR Spectroscopy. 体内核糖体放大代谢，RAMBO，实时脉冲追踪效应观察，RTPC，核磁共振波谱。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-17 Epub Date: 2025-05-27 DOI: 10.1021/acs.biochem.5c00086

Jianchao Yu, Nicholas Sciolino, Leonard Breindel, Qishan Lin, David S Burz, Alexander Shekhtman

引用次数: 0

Unique Biased Agonism Profile of βCGRP on CGRP Family Receptors. βCGRP对CGRP家族受体的独特偏倚激动作用谱。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-17 Epub Date: 2025-05-27 DOI: 10.1021/acs.biochem.4c00855

Grace Mennen, Zi Ying, Madeleine M Fletcher, Muhammad Abdur Razzak, Laura Humphrys, Tracy M Josephs, Patrick M Sexton, Denise Wootten, Peishen Zhao

{"title":"Unique Biased Agonism Profile of βCGRP on CGRP Family Receptors.","authors":"Grace Mennen, Zi Ying, Madeleine M Fletcher, Muhammad Abdur Razzak, Laura Humphrys, Tracy M Josephs, Patrick M Sexton, Denise Wootten, Peishen Zhao","doi":"10.1021/acs.biochem.4c00855","DOIUrl":"10.1021/acs.biochem.4c00855","url":null,"abstract":"α- and β-calcitonin gene-related peptides (αCGRP and βCGRP, respectively), together with adrenomedullin (AM) and AM2 are endogenous agonists of the CGRP family of receptors; CGRP receptor (CGRPR), AM1 receptor (AM1R), and AM2 receptor (AM2R). The high sequence homology and similar tissue distribution of αCGRP and βCGRP suggests they have overlapping physiological roles in pain pathways, inflammation, and metabolism, but recent data indicate potential differences in the signaling capabilities of these peptides. However, a comprehensive pharmacological characterization of βCGRP activity, compared to αCGRP, AM, and AM2 across the three CGRP family receptors, is lacking. In this study, we assessed proximal G protein coupling/activation, cognate second messenger production, regulatory protein recruitment and receptor trafficking induced by αCGRP, βCGRP, AM, and AM2 at the CGRPR, AM1R, and AM2R. Our findings revealed a distinct profile of transducer and regulatory protein engagement induced by βCGRP compared to αCGRP across these receptors. The identification of differences in pharmacological profiles for αCGRP and βCGRP indicates that they may have more distinct physiological roles than previously appreciated and may assist in distinguishing the roles of these two peptides for exploitation in targeted drug design.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"2556-2576"},"PeriodicalIF":2.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stevioside as a Neuroprotective and Anticonvulsant Agent: Insights into Its Mechanisms of Action. 甜菊糖苷作为一种神经保护和抗惊厥剂：对其作用机制的认识。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-17 Epub Date: 2025-05-28 DOI: 10.1021/acs.biochem.5c00084

Valentina Pastore, Marina Rademacher, Victoria Suarez Jaramillo, Luciana Naso, Natalia Colettis, Mariel Marder

{"title":"Stevioside as a Neuroprotective and Anticonvulsant Agent: Insights into Its Mechanisms of Action.","authors":"Valentina Pastore, Marina Rademacher, Victoria Suarez Jaramillo, Luciana Naso, Natalia Colettis, Mariel Marder","doi":"10.1021/acs.biochem.5c00084","DOIUrl":"10.1021/acs.biochem.5c00084","url":null,"abstract":"Stevia rebaudiana Bertoni, widely recognized for its natural sweetening properties, contains bioactive compounds such as stevioside (STV), which exhibit significant and multiple health benefits. This study explores the anticonvulsant properties of STV and its underlying mechanisms using in vitro and in vivo epilepsy models, focusing on its antioxidant and neuroprotective actions. In SH-SY5Y neuronal cultures, STV (10-100 μM) reversed pentylenetetrazol (PTZ)-induced damage without affecting cell viability and significantly reduced reactive oxygen species production. Electrophysiological studies in HEK293 cells expressing human voltage-gated sodium channels (hNaV1.1 or hNaV1.2) revealed that STV (100 μM) reversibly blocked sodium currents and stabilized the channels in their inactivated state, mimicking mechanisms of antiepileptic drugs. In vivo, STV (100 mg/kg, i.p. in mice) demonstrated potent anticonvulsant activity in the s.c. PTZ test, significantly reducing clonic seizure incidence, abolishing tonic-clonic seizures, and increasing latency to myoclonic events 4 h postadministration. Furthermore, STV diminished lipid peroxidation, reducing malondialdehyde levels by 30% and increasing reduced glutathione levels in brain tissue. These findings position STV as a promising candidate for epilepsy treatment, combining anticonvulsant and antioxidant properties through multifaceted mechanisms. This dual action highlights its potential as a neuroprotective agent for epilepsy and other oxidative stress-related neurological disorders.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"2611-2624"},"PeriodicalIF":2.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0