Biochemistry Biochemistry最新文献

Proteomics-Based Trapping to Study Substrates of Histone Deacetylase 6 Catalytic Domain 1. 基于蛋白质组学的组蛋白去乙酰化酶6催化结构域1底物研究

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-21 DOI: 10.1021/acs.biochem.5c00072

Udana V Ariyaratne, Valentine O Nwanelo, Rachael T Tiamiyu, Ishadi K M Kodikara, Mary Kay H Pflum

{"title":"Proteomics-Based Trapping to Study Substrates of Histone Deacetylase 6 Catalytic Domain 1.","authors":"Udana V Ariyaratne, Valentine O Nwanelo, Rachael T Tiamiyu, Ishadi K M Kodikara, Mary Kay H Pflum","doi":"10.1021/acs.biochem.5c00072","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00072","url":null,"abstract":"Histone deacetylase 6 (HDAC6) is linked with various cellular functions, such as gene expression and protein degradation, as well as many diseases, including breast cancers and Alzheimer's disease. HDAC6 removes the acetyl group of acetyllysine from histones to regulate gene expression in the nucleus. However, with predominant localization in the cytoplasm, various cytoplasmic substrates of HDAC6 have also been identified. HDAC6 is unique among the other 11 metal-dependent HDAC family members due to the presence of two independent and active deacetylase domains. Recently, an inactive mutant of HDAC6 has been used as a trap to discover substrates of the second catalytic domain (CD2). Here, substrates of the first catalytic domain (CD1) of HDAC6 were explored using trapping mutants and proteomics analysis, with 21 putative substrates identified. Among them, the E3 ubiquitin ligase HUWE1 was validated as a novel HDAC6 substrate. Specifically, E3 ligase HUWE1 was deacetylated by HDAC6 CD1 to elevate degradation activity. HDAC6 CD1 also regulated the protein levels of E3 ligase UBR5. These studies document the interplay between protein deacetylation and degradation by HDAC6 CD1, which is consistent with a model where HDAC6 CD1-mediated deacetylation influences protein degradation via E3 ligases.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339688","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 Charge of the Substrate Determines Sodium-Coupling Stoichiometry of the Amino Acid Transporter SLC6A14. 底物的电荷决定了氨基酸转运体SLC6A14的钠偶联化学计量。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-20 DOI: 10.1021/acs.biochem.5c00118

Yueyue Shi, Yang Dong, Noah B Herrington, Suhana Singh, Jiali Wang, Avner Schlessinger, Christof Grewer

{"title":"The Charge of the Substrate Determines Sodium-Coupling Stoichiometry of the Amino Acid Transporter SLC6A14.","authors":"Yueyue Shi, Yang Dong, Noah B Herrington, Suhana Singh, Jiali Wang, Avner Schlessinger, Christof Grewer","doi":"10.1021/acs.biochem.5c00118","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00118","url":null,"abstract":"SLC6A14 is a member of the SLC6 family of amino acid transporters and is known for its wide selectivity in transporting various amino acids across the cell membrane. A recent report detailed the Na+ coupling stoichiometry of SLC6A14 as 3 Na+: 1 amino acid substrate, focusing on the transport of the neutral amino acid glycine as the transported substrate. However, it is still unknown how SLC6A14 can also accommodate the transport of amino acids with positively charged side chains. Here, we employed structural modeling and multiple electrophysiological methods to investigate the unique Na+/Cl- coupling mode of SLC6A14. Our results revealed distinct, variable Na+ coupling modes when the transporter was subjected to either cationic or neutral amino acids (+, 0). In addition, our data provide further insight into the kinetic mechanism of SLC6A14, demonstrating that positively charged amino acids are transported with a 1.4- to 4-fold slower turnover rate compared to neutral amino acid substrates. We propose a binding mode in which the positively charged amino acid allows binding of and coupling of transport to only two Na+ ions, with no effect on Cl- coupling. Results from molecular dynamics (MD) simulations are consistent with this proposal. These findings have significant implications for our understanding of the substrate selectivity of the transport process as well as the development of new pharmacological compounds targeting this transporter.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332053","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 Binding of Protein l-Isoaspartyl Methyltransferase (PIMT) to Tubulin and Disruption of Microtubule Assembly Leading to Tumor Regression. 蛋白l-异天冬氨酸甲基转移酶（PIMT）与微管蛋白的结合和微管组装的破坏导致肿瘤消退。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-20 DOI: 10.1021/acs.biochem.5c00087

Tanaya Chatterjee, Rimi Mukherjee, Gaurav Das, Arumay Pal, Sudipta Bag, Barun K Chatterjee, Pinak Chakrabarti

{"title":"The Binding of Protein l-Isoaspartyl Methyltransferase (PIMT) to Tubulin and Disruption of Microtubule Assembly Leading to Tumor Regression.","authors":"Tanaya Chatterjee, Rimi Mukherjee, Gaurav Das, Arumay Pal, Sudipta Bag, Barun K Chatterjee, Pinak Chakrabarti","doi":"10.1021/acs.biochem.5c00087","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00087","url":null,"abstract":"Microtubules, the key component of the cytoskeleton, are indispensable for various cellular tasks such as cell differentiation, mitosis, etc. Disruption of microtubule assembly plays a crucial role in tumor regulation. Protein l-isoaspartyl methyltransferase (PIMT), found in abundance in brain, is known to repair abnormal isoaspartate residues, formed on aging, to the normal aspartate. Using various biophysical techniques, we show that PIMT can compromise the microtubule network after internalization in cells. The binding of PIMT to tubulin overlaps with the vinblastine binding site, as inferred from the competitive assay. Experiments using MCF-7 breast cancer cells revealed the binding of PIMT with intracellular tubulin and the disruption of the network. Results are reproducible in an additional breast cancer cell line, MDA-MB-231. In vivo experiments using mice with breast cancer cells revealed tumor regression after treatment with PIMT. Like other antimitotic agents, PIMT can target tubulin, regulating the structure and dynamics of microtubules. The free energy of binding of PIMT to tubulin was found to be -6.3 kcal/mol obtained from Isothermal Titration Calorimetry (ITC). The PIMT-tubulin complex structure determined by AlphaFold suggests an interface that overlays considerably with that between two tubulin heterodimers in the microtubule, suggesting a mechanism by which the binding of PIMT can induce the dissociation of the microtubule. Asp/Asn residues present at the latter interface would be subjected to various degrees of isomerization and thereby control the properties and functions of the microtubule and also be a substrate for the repair enzyme, PIMT.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336116","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

Determining Factors for Spermidine-Induced Modulation of Conformational Stability and Dynamics of Horse Myoglobin. 亚精胺诱导的马肌红蛋白构象稳定性和动力学调节的决定因素。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-20 DOI: 10.1021/acs.biochem.5c00033

Manisha Yadav, Sureshan Muthusamy, Saraboji Kadhirvel, Deepak Sharma, Rajesh Kumar

{"title":"Determining Factors for Spermidine-Induced Modulation of Conformational Stability and Dynamics of Horse Myoglobin.","authors":"Manisha Yadav, Sureshan Muthusamy, Saraboji Kadhirvel, Deepak Sharma, Rajesh Kumar","doi":"10.1021/acs.biochem.5c00033","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00033","url":null,"abstract":"The present work describes how water-miscible natural polyamine (NPA) spermidine (SPD) alters the conformational stability and dynamics of horse myoglobin (h-Mb) at pH 7.4. Analysis of thermal- and chemical-induced unfolding profiles of h-Mb at different concentrations of SPD at pH 7.4 revealed that SPD (≥5 mM) reduces the conformational stability of h-Mb. The effect of SPD was further corroborated using MD simulations, which showed that SPD (≥5 mM) enhanced the conformational fluctuations and reduced the structural stability of h-Mb. The SPD concentration effect on the thermodynamic equilibria (KU) of h-Mb was translated to the changes in preferential interaction coefficient (ΔΓ23) and hydration number (ΔΓw). The finding of the positive value of ΔΓ23 and the negative value of ΔΓw suggests that the interaction of SPD with h-Mb and the exclusion of water from the protein reduce the conformational stability of h-Mb. Analysis of SPD effects on enthalpy-entropy plots and temperature dependence of unfolding free energy of h-Mb suggests that the SPD forms soft, attractive enthalpic interactions with h-Mb. Analysis of SPD impact on the urea-concentration-dependent thermal unfolding midpoint temperature showed that SPD exhibits an additive effect to the urea-mediated decrease in the thermal stability of h-Mb.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332052","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 Tight-Knit Family: The Medium-Chain Dehydrogenase/Reductases of Monoterpene Indole Alkaloid Biosynthesis. 一个紧密结合的家族：单萜吲哚生物碱生物合成的中链脱氢酶/还原酶。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-19 DOI: 10.1021/acs.biochem.5c00234

Samuel C Carr, Sarah E O'Connor

引用次数: 0

A Pair of Promiscuous Surrogates for N-Acetyl-l-Glutamate Synthase, the Initial Enzyme of Bacterial Arginine Biosynthesis. 细菌精氨酸生物合成初始酶n -乙酰-l-谷氨酸合成酶的一对混杂替代物。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-19 DOI: 10.1021/acs.biochem.5c00054

Carley Z Reid, Allison N Dombroski, Vitalii S Basistyi, Kevin K Desai, Brian G Miller

{"title":"A Pair of Promiscuous Surrogates for N-Acetyl-l-Glutamate Synthase, the Initial Enzyme of Bacterial Arginine Biosynthesis.","authors":"Carley Z Reid, Allison N Dombroski, Vitalii S Basistyi, Kevin K Desai, Brian G Miller","doi":"10.1021/acs.biochem.5c00054","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00054","url":null,"abstract":"The identification and characterization of promiscuous enzymes is significant because they provide the raw materials for evolving new catalysts and assembling new metabolic pathways. Here, we report the discovery of two promiscuous enzymes from Escherichia coli capable of synthesizing N-acetyl-l-glutamate, the first metabolic intermediate in bacterial arginine biosynthesis. The catalytic subunit of aspartate transcarbamoylase (PyrB) and p-aminobenzoyl-glutamate hydrolase (AbgAB) catalyze the acetyl phosphate-dependent acetylation of l-glutamate with catalytic efficiencies (kcat/Km, glutamate) of 0.089 and 0.59 M-1 s-1, respectively. Although the promiscuous activities of PyrB and AbgAB are over 105 -fold lower than the native E. coli N-acetyl-l-glutamate synthase (ArgA), both can function via multicopy suppression to restore growth to an argA-deficient auxotroph on glucose minimal medium. We also describe a pair of spontaneous chromosomal mutations in the acetate kinase gene that facilitate PyrB-mediated replacement of ArgA. These nonsynonymous substitutions encode two variants, D248E and L279Q, that display ∼130-fold and ∼920-fold reductions in acetate kinase activity, respectively. Past work demonstrates that inactivation of acetate kinase leads to intracellular accumulation of acetyl phosphate, suggesting the observed mutations function by boosting the concentration of this noncanonical PyrB substrate. This work provides the first report of promiscuous N-acetyl-l-glutamate synthases and demonstrates how secondary, loss-of-function mutations can tune metabolism such that previously irrelevant latent activities may be elevated from physiological obscurity to an essential role in biosynthesis following overproduction.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323826","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

Proline-Aromatic Sequences Stabilize Turns via C-H/π Interactions in Both cis-Proline and trans-Proline. 脯氨酸-芳香族序列通过C-H/π相互作用稳定顺式脯氨酸和反式脯氨酸的旋转。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-18 DOI: 10.1021/acs.biochem.5c00144

Himal K Ganguly, Michael B Elbaum, Neal J Zondlo

{"title":"Proline-Aromatic Sequences Stabilize Turns via C-H/π Interactions in Both cis-Proline and trans-Proline.","authors":"Himal K Ganguly, Michael B Elbaum, Neal J Zondlo","doi":"10.1021/acs.biochem.5c00144","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00144","url":null,"abstract":"In proteins, proline-aromatic sequences exhibit increased frequencies of cis-proline amide bonds, via proposed C-H/π interactions between the aromatic ring and either the proline ring or the backbone C-Hα of the residue prior to proline. However, previous bioinformatics studies on proteins and experiments on proline-aromatic sequences in peptides have not revealed a clear correlation between the electronic properties of the aromatic ring and the population of cis-proline. An investigation of the effects of aromatic residue on the conformation of proline-aromatic sequences was conducted using three approaches: NMR spectroscopy in model peptides of the sequence Ac-TGPAr-NH2 (Ar = encoded and unnatural aromatic amino acids); bioinformatics analysis of structures in proline-aromatic sequences in the PDB; and quantum computational investigations. C-H/π and hydrophobic interactions were observed to stabilize local structures in both the trans-proline and cis-proline conformations, with each exhibiting C-H/π interactions between the aromatic ring and Hα of the residue prior to proline and/or with the proline ring. These C-H/π interactions were strongest with tryptophan and weakest with cationic histidine. Aromatic interactions with histidine were modulated in strength by His ionization state. Proline-aromatic sequences were associated with specific conformational poses, including type I and type VI β-turns. C-H/π interactions at the pre-proline Hα, which were stronger than interactions at Pro, stabilize normally less favorable conformations, including the ζ or αL conformations at the pre-proline residue, cis-proline, and/or the g+ χ1 rotamer or αL conformation at the aromatic residue. Proline-aromatic sequences, especially Pro-Trp sequences, are loci to nucleate turns, helices, loops, and other local structures in proteins.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315474","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

Distinct Protochromic Mechanisms Driving Green/Red Absorption in Phycocyanobilin-Binding Proteins. 藻蓝胆素结合蛋白中绿色/红色吸收的不同原色机制

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2025-06-18 DOI: 10.1021/acs.biochem.4c00870

Tomoyasu Noji, Keisuke Saito, Hiroshi Ishikita

{"title":"Distinct Protochromic Mechanisms Driving Green/Red Absorption in Phycocyanobilin-Binding Proteins.","authors":"Tomoyasu Noji, Keisuke Saito, Hiroshi Ishikita","doi":"10.1021/acs.biochem.4c00870","DOIUrl":"https://doi.org/10.1021/acs.biochem.4c00870","url":null,"abstract":"RcaE, a phycocyanobilin (PCB)-binding protein, undergoes a reversible structural conversion, shifting light absorption between red (Pr-state) and green (Pg-state). Using a quantum mechanical/molecular mechanical approach combined with a linear Poisson-Boltzmann equation, we reveal the molecular mechanisms underlying this 130 nm blue shift. The experimentally measured Pg-RcaE absorption wavelength is reproduced only when ring B of PCB is deprotonated. While the low-dielectric chromophore environment remains unchanged during the Pr-to-Pg conversion, Lys261 deprotonation in Pg-RcaE is driven by the loss of key electrostatic interactions, specifically the loss of salt bridges with PCB propionic groups. Unlike Slr1393g3, where a 110 nm blue shift arises from PCB conformational changes, RcaE employs a distinct mechanism, leveraging proton-mediated electrostatic changes while maintaining a low-dielectric environment. This Pr-to-Pg conversion is triggered by ring B deprotonation via Glu217, facilitated by water molecules forming a Grotthuss-like proton transfer pathway. This unique strategy achieves efficient photochromic switching and a large spectral shift without PCB structural rearrangements.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323841","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

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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178251/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0