Biochemistry Biochemistry最新文献_第3页

¹⁹F NMR Reveals the Dynamics of Substrate Binding and Lid Closure for Iodotyrosine Deiodinase as a Complement to Steady-State Kinetics and Crystallography. 19F NMR 揭示碘酪氨酸脱碘酶的底物结合和盖闭的动力学过程，作为对稳态动力学和晶体学的补充。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2024-09-03 Epub Date: 2024-08-13 DOI: 10.1021/acs.biochem.4c00243

Harrison C Greenberg, Ananya Majumdar, Ekroop Kaur Cheema, Anton Kozyryev, Steven E Rokita

{"title":"19F NMR Reveals the Dynamics of Substrate Binding and Lid Closure for Iodotyrosine Deiodinase as a Complement to Steady-State Kinetics and Crystallography.","authors":"Harrison C Greenberg, Ananya Majumdar, Ekroop Kaur Cheema, Anton Kozyryev, Steven E Rokita","doi":"10.1021/acs.biochem.4c00243","DOIUrl":"10.1021/acs.biochem.4c00243","url":null,"abstract":"Active site lids are common features of enzymes and typically undergo conformational changes upon substrate binding to promote catalysis. Iodotyrosine deiodinase is no exception and contains a lid segment in all of its homologues from human to bacteria. The solution-state dynamics of the lid have now been characterized using 19F NMR spectroscopy with a CF3-labeled enzyme and CF3O-labeled ligands. From two-dimensional 19F-19F NMR exchange spectroscopy, interconversion rates between the free and bound states of a CF3O-substituted tyrosine (45 ± 10 s-1) and the protein label (40 ± 3 s-1) are very similar and suggest a correlation between ligand binding and conformational reorganization of the lid. Both occur at rates that are ∼100-fold faster than turnover, and therefore these steps do not limit catalysis. A simple CF3O-labeled phenol also binds to the active site and induces a conformational change in the lid segment that was not previously detectable by crystallography. Exchange rates of the ligand (130 ± 20 s-1) and protein (98 ± 8 s-1) in this example are faster than those above but remain self-consistent to affirm a correlation between ordering of the lid and binding of the ligand. Both ligands also protect the protein from limited proteolysis, as expected from their ability to stabilize a compact lid structure. However, the minimal turnover of simple phenol substrates indicates that such stabilization may be necessary but is not sufficient for efficient catalysis.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974412","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

Correction to "Trifluoroethanol Promotes Helix Formation by Destabilizing Backbone Exposure: Desolvation Rather than Native Hydrogen Bonding Defines the Kinetic Pathway of Dimeric Coiled Coil Folding". 更正 "三氟乙醇通过破坏骨架暴露的稳定性促进螺旋的形成：脱溶而不是原生氢键定义了二聚盘绕线圈折叠的动力学途径"。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2024-09-03 Epub Date: 2024-08-14 DOI: 10.1021/acs.biochem.4c00426

Alex Kentsis, Tobin R Sosnick

引用次数: 0

¹⁹F Fast Magic-Angle Spinning NMR Spectroscopy on Microcrystalline Complexes of Fluorinated Ligands and the Carbohydrate Recognition Domain of Galectin-3. 19F 快速魔角旋转核磁共振波谱分析含氟配体与 Galectin-3 碳水化合物识别域的微晶复合物。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2024-09-03 Epub Date: 2024-07-15 DOI: 10.1021/acs.biochem.4c00232

Roza Kalabekova, Caitlin M Quinn, Kumar Tekwani Movellan, Angela M Gronenborn, Mikael Akke, Tatyana Polenova

引用次数: 0

Allosteric Communication of the Dimerization and the Catalytic Domain in Photoreceptor Guanylate Cyclase. 感光器鸟苷酸环化酶二聚体和催化域的异构通讯

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2024-09-03 Epub Date: 2024-08-23 DOI: 10.1021/acs.biochem.4c00170

Manisha Kumari Shahu, Fabian Schuhmann, Siu Ying Wong, Ilia A Solov'yov, Karl-Wilhelm Koch

{"title":"Allosteric Communication of the Dimerization and the Catalytic Domain in Photoreceptor Guanylate Cyclase.","authors":"Manisha Kumari Shahu, Fabian Schuhmann, Siu Ying Wong, Ilia A Solov'yov, Karl-Wilhelm Koch","doi":"10.1021/acs.biochem.4c00170","DOIUrl":"10.1021/acs.biochem.4c00170","url":null,"abstract":"Phototransduction in vertebrate photoreceptor cells is controlled by Ca2+-dependent feedback loops involving the membrane-bound guanylate cyclase GC-E that synthesizes the second messenger guanosine-3',5'-cyclic monophosphate. Intracellular Ca2+-sensor proteins named guanylate cyclase-activating proteins (GCAPs) regulate the activity of GC-E by switching from a Ca2+-bound inhibiting state to a Ca2+-free/Mg2+-bound activating state. The gene GUCY2D encodes for human GC-E, and mutations in GUCY2D are often associated with an imbalance of Ca2+ and cGMP homeostasis causing retinal disorders. Here, we investigate the Ca2+-dependent inhibition of the constitutively active GC-E mutant V902L. The inhibition is not mediated by GCAP variants but by Ca2+ replacing Mg2+ in the catalytic center. Distant from the cyclase catalytic domain is an α-helical domain containing a highly conserved helix-turn-helix motif. Mutating the critical amino acid position 804 from leucine to proline left the principal activation mechanism intact but resulted in a lower level of catalytic efficiency. Our experimental analysis of amino acid positions in two distant GC-E domains implied an allosteric communication pathway connecting the α-helical and the cyclase catalytic domains. A computational connectivity analysis unveiled critical differences between wildtype GC-E and the mutant V902L in the allosteric network of critical amino acid positions.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034455","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

Poly-GR Impairs PRMT1-Mediated Arginine Methylation of Disease-Linked RNA-Binding Proteins by Acting as a Substrate Sink. Poly-GR通过充当底物汇削弱了PRMT1介导的与疾病相关的RNA结合蛋白的精氨酸甲基化。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2024-09-03 Epub Date: 2024-08-15 DOI: 10.1021/acs.biochem.4c00308

Saskia Hutten, Jia-Xuan Chen, Adrian M Isaacs, Dorothee Dormann

{"title":"Poly-GR Impairs PRMT1-Mediated Arginine Methylation of Disease-Linked RNA-Binding Proteins by Acting as a Substrate Sink.","authors":"Saskia Hutten, Jia-Xuan Chen, Adrian M Isaacs, Dorothee Dormann","doi":"10.1021/acs.biochem.4c00308","DOIUrl":"10.1021/acs.biochem.4c00308","url":null,"abstract":"Dipeptide repeat proteins (DPRs) are aberrant protein species found in C9orf72-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two neurodegenerative diseases characterized by the cytoplasmic mislocalization and aggregation of RNA-binding proteins (RBPs). In particular, arginine (R)-rich DPRs (poly-GR and poly-PR) have been suggested to promiscuously interact with multiple cellular proteins and thereby exert high cytotoxicity. Components of the protein arginine methylation machinery have been identified as modulators of DPR toxicity and/or potential cellular interactors of R-rich DPRs; however, the molecular details and consequences of such an interaction are currently not well understood. Here, we demonstrate that several members of the family of protein arginine methyltransferases (PRMTs) can directly interact with R-rich DPRs in vitro and in the cytosol. In vitro, R-rich DPRs reduce solubility and promote phase separation of PRMT1, the main enzyme responsible for asymmetric arginine-dimethylation (ADMA) in mammalian cells, in a concentration- and length-dependent manner. Moreover, we demonstrate that poly-GR interferes more efficiently than poly-PR with PRMT1-mediated arginine methylation of RBPs such as hnRNPA3. We additionally show by two alternative approaches that poly-GR itself is a substrate for PRMT1-mediated arginine dimethylation. We propose that poly-GR may act as a direct competitor for arginine methylation of cellular PRMT1 targets, such as disease-linked RBPs.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986749","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

IGF2BP1-Mediated Regulation of CCN1 Expression by Specific Binding to G-Quadruplex Structure in Its 3'UTR. IGF2BP1 通过与 CCN1 3'UTR 中的 G-四链结构特异性结合来调节 CCN1 的表达。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2024-09-03 Epub Date: 2024-08-12 DOI: 10.1021/acs.biochem.4c00172

Priya Rana, Rajat Ujjainiya, Vishal Bharti, Souvik Maiti, Mary K Ekka

{"title":"IGF2BP1-Mediated Regulation of CCN1 Expression by Specific Binding to G-Quadruplex Structure in Its 3'UTR.","authors":"Priya Rana, Rajat Ujjainiya, Vishal Bharti, Souvik Maiti, Mary K Ekka","doi":"10.1021/acs.biochem.4c00172","DOIUrl":"10.1021/acs.biochem.4c00172","url":null,"abstract":"The intricate regulation of gene expression is fundamental to the biological complexity of higher organisms, and is primarily governed by transcriptional and post-transcriptional mechanisms. The 3'-untranslated region (3'UTR) of mRNA is rich in cis-regulatory elements like G-quadruplexes (G4s), and plays a crucial role in post-transcriptional regulation. G4s have emerged as significant gene regulators, impacting mRNA stability, translation, and localization. In this study, we investigate the role of a robust parallel G4 structure situated within the 3'UTR of CCN1 mRNA in post-transcriptional regulation. This G4 structure is proximal to the stop codon of human CCN1, and evolutionarily conserved. We elucidated its interaction with the insulin-like growth factor 2 binding protein 1 (IGF2BP1), a noncanonical RNA N6-methyladenosine (m6A) modification reader, revealing a novel interplay between RNA modifications and G-quadruplex structures. Knockdown experiments and mutagenesis studies demonstrate that IGF2BP1 binds specifically to the G4 structure, modulating CCN1 mRNA stability. Additionally, we unveil the role of IGF2BP1's RNA recognition motifs in G4 recognition, highlighting this enthalpically driven interaction. Our findings offer fresh perspectives on the complex mechanisms of post-transcriptional gene regulation mediated by G4 RNA secondary structures.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915424","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

Biosynthetic Strategies of Berberine Bridge Enzyme-like Flavoprotein Oxidases toward Structural Diversification in Natural Product Biosynthesis. 小檗碱桥酶样黄酮蛋白氧化酶的生物合成策略，实现天然产物生物合成的结构多样化。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2024-09-03 Epub Date: 2024-08-12 DOI: 10.1021/acs.biochem.4c00320

Gwen Tjallinks, Andrea Mattevi, Marco W Fraaije

{"title":"Biosynthetic Strategies of Berberine Bridge Enzyme-like Flavoprotein Oxidases toward Structural Diversification in Natural Product Biosynthesis.","authors":"Gwen Tjallinks, Andrea Mattevi, Marco W Fraaije","doi":"10.1021/acs.biochem.4c00320","DOIUrl":"10.1021/acs.biochem.4c00320","url":null,"abstract":"Berberine bridge enzyme-like oxidases are often involved in natural product biosynthesis and are seen as essential enzymes for the generation of intricate pharmacophores. These oxidases have the ability to transfer a hydride atom to the FAD cofactor, which enables complex substrate modifications and rearrangements including (intramolecular) cyclizations, carbon-carbon bond formations, and nucleophilic additions. Despite the diverse range of activities, the mechanistic details of these reactions often remain incompletely understood. In this Review, we delve into the complexity that BBE-like oxidases from bacteria, fungal, and plant origins exhibit by providing an overview of the shared catalytic features and emphasizing the different reactivities. We propose four generalized modes of action by which BBE-like oxidases enable the synthesis of natural products, ranging from the classic alcohol oxidation reactions to less common amine and amide oxidation reactions. Exploring the mechanisms utilized by nature to produce its vast array of natural products is a subject of considerable interest and can lead to the discovery of unique biochemical activities.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141969975","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

Enzyme Catalyzed Formation of CoA Adducts of Fluorinated Hexanoic Acid Analogues using a Long-Chain acyl-CoA Synthetase from Gordonia sp. Strain NB4-1Y. 利用戈登氏菌菌株 NB4-1Y 的长链酰基-CoA 合成酶催化氟化己酸类似物 CoA 加合物的形成。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2024-09-03 Epub Date: 2024-08-17 DOI: 10.1021/acs.biochem.4c00336

Robert G Mothersole, Mina K Mothersole, Hannah G Goddard, Jinxia Liu, Jonathan D Van Hamme

{"title":"Enzyme Catalyzed Formation of CoA Adducts of Fluorinated Hexanoic Acid Analogues using a Long-Chain acyl-CoA Synthetase from Gordonia sp. Strain NB4-1Y.","authors":"Robert G Mothersole, Mina K Mothersole, Hannah G Goddard, Jinxia Liu, Jonathan D Van Hamme","doi":"10.1021/acs.biochem.4c00336","DOIUrl":"10.1021/acs.biochem.4c00336","url":null,"abstract":"Per and polyfluoroalkyl substances (PFAS) are a large family of anthropogenic fluorinated chemicals of increasing environmental concern. Over recent years, numerous microbial communities have been found to be capable of metabolizing some polyfluoroalkyl substances, generating a range of low-molecular-weight PFAS metabolites. One proposed pathway for the microbial breakdown of fluorinated carboxylates includes β-oxidation, this pathway is initiated by the formation of a CoA adduct. However, until recently no PFAS-CoA adducts had been reported. In a previous study, we were able to use a bacterial medium-chain acyl-CoA synthetase (mACS) to form CoA adducts of fluorinated adducts of propanoic acid and pentanoic acid but were not able to detect any products of fluorinated hexanoic acid analogues. Herein, we expressed and purified a long-chain acyl-CoA synthetase (lACS) and a A461K variant of mACS from the soil bacterium Gordonia sp. strain NB4-1Y and performed an analysis of substrate scope and enzyme kinetics using fluorinated and nonfluorinated carboxylates. We determined that lACS can catalyze the formation of CoA adducts of 1:5 fluorotelomer carboxylic acid (FTCA), 2:4 FTCA and 3:3 FTCA, albeit with generally low turnover rates (<0.02 s-1) compared with the nonfluorinated hexanoic acid (5.39 s-1). In addition, the A461K variant was found to have an 8-fold increase in selectivity toward hexanoic acid compared with wild-type mACS, suggesting that Ala-461 has a mechanistic role in selectivity toward substrate chain length. This provides further evidence to validate the proposed activation step involving the formation of CoA adducts in the enzymatic breakdown of PFAS.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994800","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

Structural Basis of Substrate Recognition by the Postmitosane Modification Enzyme MitM in Mitomycin Biosynthesis. 在丝裂霉素生物合成过程中，后mitosane修饰酶MitM识别底物的结构基础。

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2024-09-03 Epub Date: 2024-08-14 DOI: 10.1021/acs.biochem.4c00330

Danna Dong, Mingyu Xia, Sili Wang, Pengfei Fang, Wen Liu

{"title":"Structural Basis of Substrate Recognition by the Postmitosane Modification Enzyme MitM in Mitomycin Biosynthesis.","authors":"Danna Dong, Mingyu Xia, Sili Wang, Pengfei Fang, Wen Liu","doi":"10.1021/acs.biochem.4c00330","DOIUrl":"10.1021/acs.biochem.4c00330","url":null,"abstract":"Mitomycins make up a class of natural molecules produced by Streptomyces with strong antibacterial and antitumor activities. MitM is a key postmitosane modification enzyme involved in mitomycin biosynthesis in Streptomyces caespitosus. This protein was previously suggested to catalyze the aziridinium methylation of mitomycin A and the mitomycin intermediate 9a-demethyl-mitomycin A as an N-methyltransferase. The structural basis for MitM to recognize cofactor S-adenosyl-l-methionine (SAM) and substrate mitomycin A is unknown. Here, we determined the crystal structures of apo-MitM and MitM-mitomycin A-S-adenosylhomocysteine (SAH) ternary complexes with resolutions of 2.23 and 2.80 Å, respectively. We found that MitM adopts a class I SAM-dependent methyltransferase fold and forms a homodimer in solution. Conformational changes in a series of residues involved in the formation of active pockets assist MitM in binding SAH and mitomycin A. In particular, the 28ALGAASLGE36 loop changes most significantly. When mitomycin A binds, the bending direction of this loop is reversed, changing the entrance of the active site from open to closed. This study provides structural insights into MitM's involvement in the postmitosane stage of mitomycin biosynthesis and provides a template for the engineering of methyltransferases.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981172","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

Insights into the Interaction Landscape of the EVH1 Domain of Mena. 洞察 Mena 的 EVH1 结构域的相互作用格局

IF 2.9 3区生物学

Biochemistry Biochemistry Pub Date : 2024-09-03 Epub Date: 2024-08-13 DOI: 10.1021/acs.biochem.4c00331

Lanette LaComb, Agnidipta Ghosh, Jeffrey B Bonanno, Daniel J Nilson, Alex J Poppel, Lucas Dada, Sean M Cahill, Juan Pablo Maianti, Seiya Kitamura, David Cowburn, Steven C Almo

{"title":"Insights into the Interaction Landscape of the EVH1 Domain of Mena.","authors":"Lanette LaComb, Agnidipta Ghosh, Jeffrey B Bonanno, Daniel J Nilson, Alex J Poppel, Lucas Dada, Sean M Cahill, Juan Pablo Maianti, Seiya Kitamura, David Cowburn, Steven C Almo","doi":"10.1021/acs.biochem.4c00331","DOIUrl":"10.1021/acs.biochem.4c00331","url":null,"abstract":"The Enabled/VASP homology 1 (EVH1) domain is a small module that interacts with proline-rich stretches in its ligands and is found in various signaling and scaffolding proteins. Mena, the mammalian homologue of Ena, is involved in diverse actin-associated events, such as membrane dynamics, bacterial motility, and tumor intravasation and extravasation. Two-dimensional (2D) 1H-15N HSQC NMR was used to study Mena EVH1 binding properties, defining the amino acids involved in ligand recognition for the physiological ligands ActA and PCARE, and a synthetic polyproline-inspired small molecule (hereafter inhibitor 6c). Chemical shift perturbations indicated that proline-rich segments bind in the conserved EVH1 hydrophobic cleft. The PCARE-derived peptide elicited more perturbations compared to the ActA-derived peptide, consistent with a previous report of a structural alteration in the solvent-exposed β7-β8 loop. Unexpectedly, EVH1 and the proline-rich segment of PTP1B did not exhibit NMR chemical shift perturbations; however, the high-resolution crystal structure implicated the conserved EVH1 hydrophobic cleft in ligand recognition. Intrinsic steady-state fluorescence and fluorescence polarization assays indicate that residues outside the proline-rich segment enhance the ligand affinity for EVH1 (Kd = 3-8 μM). Inhibitor 6c displayed tighter binding (Kd ∼ 0.3 μM) and occupies the same EVH1 cleft as physiological ligands. These studies revealed that the EVH1 domain enhances ligand affinity through recognition of residues flanking the proline-rich segments. Additionally, a synthetic inhibitor binds more tightly to the EVH1 domain than natural ligands, occupying the same hydrophobic cleft.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974414","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