Protein Engineering Design & Selection最新文献_第3页

Engineering the enzyme toolbox to tailor glycosylation in small molecule natural products and protein biologics. 设计酶工具箱，以定制小分子天然产物和蛋白质生物制品的糖基化。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2023-01-21 DOI: 10.1093/protein/gzac010

Sara Ouadhi, Dulce María Valdez López, F Ifthiha Mohideen, David H Kwan

{"title":"Engineering the enzyme toolbox to tailor glycosylation in small molecule natural products and protein biologics.","authors":"Sara Ouadhi, Dulce María Valdez López, F Ifthiha Mohideen, David H Kwan","doi":"10.1093/protein/gzac010","DOIUrl":"https://doi.org/10.1093/protein/gzac010","url":null,"abstract":"Many glycosylated small molecule natural products and glycoprotein biologics are important in a broad range of therapeutic and industrial applications. The sugar moieties that decorate these compounds often show a profound impact on their biological functions, thus biocatalytic methods for controlling their glycosylation are valuable. Enzymes from nature are useful tools to tailor bioproduct glycosylation but these sometimes have limitations in their catalytic efficiency, substrate specificity, regiospecificity, stereospecificity, or stability. Enzyme engineering strategies such as directed evolution or semi-rational and rational design have addressed some of the challenges presented by these limitations. In this review, we highlight some of the recent research on engineering enzymes to tailor the glycosylation of small molecule natural products (including alkaloids, terpenoids, polyketides, and peptides), as well as the glycosylation of protein biologics (including hormones, enzyme-replacement therapies, enzyme inhibitors, vaccines, and antibodies).","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":"36 ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10592744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1

Effect of alanine versus serine at position 88 of human transthyretin mutants on the protein stability. 人转甲状腺素突变体88位丙氨酸和丝氨酸对蛋白质稳定性的影响。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2023-01-21 DOI: 10.1093/protein/gzad001

Kyung-Hoon Lee, Krzysztof Kuczera

{"title":"Effect of alanine versus serine at position 88 of human transthyretin mutants on the protein stability.","authors":"Kyung-Hoon Lee, Krzysztof Kuczera","doi":"10.1093/protein/gzad001","DOIUrl":"https://doi.org/10.1093/protein/gzad001","url":null,"abstract":"Human transthyretin (TTR) is a homo-tetrameric plasma protein associated with a high percentage of β-sheet forming amyloid fibrils. It accumulates in tissues or extracellular matrices to cause amyloid diseases. Free energy simulations with thermodynamic integration based on all-atom molecular dynamics simulations have been carried out to analyze the effects of the His88 → Ala and Ser mutations on the stability of human TTR. The calculated free energy change differences (ΔΔG) caused by the His88 → Ala and His88 → Ser mutations are -1.84 ± 0.86 and 7.56 ± 0.55 kcal/mol, respectively, which are in excellent agreement with prior reported experimental values. The simulation results show that the H88A mutant is more stable than the wild type, whereas the H88S mutant is less stable than the wild type. The free energy component analysis shows that the contribution to the free energy change difference (ΔΔG) for the His88 → Ala and His88 → Ser mutations mainly arise from electrostatic and van der Waals interactions, respectively. The electrostatic term stabilizes the H88A mutant more than the wild type, but the van der Waals interaction destabilizes the H88S mutant relative to the wild type. Individual residue contributions to the free energy change show neighboring residues exert stabilizing and destabilizing influence on the mutants. The implications of the simulation results for understanding the stabilizing and destabilizing effect and its contribution to protein stability are discussed.","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":"36 ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9125553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Engineering enzyme activity using an expanded amino acid alphabet. 利用扩展的氨基酸字母表工程酶活性。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2023-01-21 DOI: 10.1093/protein/gzac013

Zachary Birch-Price, Christopher J Taylor, Mary Ortmayer, Anthony P Green

引用次数: 3

abYpap: improvements to the prediction of antibody VH/VL packing using gradient boosted regression. abYpap:使用梯度增强回归预测抗体V H/V L包装的改进。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2023-01-21 DOI: 10.1093/protein/gzad021

Veronica A Boron, Andrew C R Martin

引用次数: 0

Engineering cellulases for conversion of lignocellulosic biomass. 转化木质纤维素生物质的纤维素酶工程。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2023-01-21 DOI: 10.1093/protein/gzad002

Yogesh B Chaudhari, Anikó Várnai, Morten Sørlie, Svein J Horn, Vincent G H Eijsink

引用次数: 0

Engineering Candida boidinii formate dehydrogenase for activity with the non-canonical cofactor 3'-NADP(H). 利用非经典辅因子3'-NADP（H）对博伊迪尼假丝酵母甲酸脱氢酶进行活性改造。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2023-01-21 DOI: 10.1093/protein/gzad009

Salomon Vainstein, Scott Banta

{"title":"Engineering Candida boidinii formate dehydrogenase for activity with the non-canonical cofactor 3'-NADP(H).","authors":"Salomon Vainstein, Scott Banta","doi":"10.1093/protein/gzad009","DOIUrl":"10.1093/protein/gzad009","url":null,"abstract":"Oxidoreductases catalyze essential redox reactions, and many require a diffusible cofactor for electron transport, such as NAD(H). Non-canonical cofactor analogs have been explored as a means to create enzymatic reactions that operate orthogonally to existing metabolism. Here, we aimed to engineer the formate dehydrogenase from Candid boidinii (CbFDH) for activity with the non-canonical cofactor nicotinamide adenine dinucleotide 3'-phosphate (3'-NADP(H)). We used PyRosetta, the Cofactor Specificity Reversal Structural Analysis and Library Design (CSR-SALAD), and structure-guided saturation mutagenesis to identify mutations that enable CbFDH to use 3'-NADP+. Two single mutants, D195A and D195G, had the highest activities with 3'-NADP+, while the double mutant D195G/Y196S exhibited the highest cofactor selectivity reversal behavior. Steady state kinetic analyses were performed; the D195A mutant exhibited the highest KTS value with 3'-NADP+. This work compares the utility of computational approaches for cofactor specificity engineering while demonstrating the engineering of an important enzyme for novel non-canonical cofactor selectivity.","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10146296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Masked inverse folding with sequence transfer for protein representation learning. 用于蛋白质表示学习的带序列转移的掩模反向折叠。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2023-01-21 DOI: 10.1093/protein/gzad015

Kevin K Yang, Niccolò Zanichelli, Hugh Yeh

引用次数: 0

Engineering of a phosphotriesterase with improved stability and enhanced activity for detoxification of the pesticide metabolite malaoxon. 一种具有改进的稳定性和增强的农药代谢产物马拉氧酮解毒活性的磷酸三酯酶的工程。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2023-01-21 DOI: 10.1093/protein/gzad020

Laura Job, Anja Köhler, Mauricio Testanera, Benjamin Escher, Franz Worek, Arne Skerra

{"title":"Engineering of a phosphotriesterase with improved stability and enhanced activity for detoxification of the pesticide metabolite malaoxon.","authors":"Laura Job, Anja Köhler, Mauricio Testanera, Benjamin Escher, Franz Worek, Arne Skerra","doi":"10.1093/protein/gzad020","DOIUrl":"10.1093/protein/gzad020","url":null,"abstract":"Organophosphorus (OP) pesticides are still widely applied but pose a severe toxicological threat if misused. For in vivo detoxification, the application of hydrolytic enzymes potentially offers a promising treatment. A well-studied example is the phosphotriesterase of Brevundimonas diminuta (BdPTE). Whereas wild-type BdPTE can hydrolyse pesticides like paraoxon, chlorpyrifos-oxon and mevinphos with high catalytic efficiencies, kcat/KM >2 × 107 M-1 min-1, degradation of malaoxon is unsatisfactory (kcat/KM ≈ 1 × 104 M-1 min-1). Here, we report the rational engineering of BdPTE mutants with improved properties and their efficient production in Escherichia coli. As result, the mutant BdPTE(VRNVVLARY) exhibits 37-fold faster malaoxon hydrolysis (kcat/KM = 4.6 × 105 M-1 min-1), together with enhanced expression yield, improved thermal stability and reduced susceptibility to oxidation. Therefore, this BdPTE mutant constitutes a powerful candidate to develop a biocatalytic antidote for the detoxification of this common pesticide metabolite as well as related OP compounds.","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71523393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Correction to: The variable conversion of neutralizing anti-SARS-CoV-2 single-chain antibodies to IgG provides insight into RBD epitope accessibility. 更正：中和抗严重急性呼吸系统综合征冠状病毒2型单链抗体向IgG的可变转化提供了对RBD表位可及性的深入了解。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2023-01-21 DOI: 10.1093/protein/gzad018

引用次数: 0

Non-canonical amino acids as a tool for the thermal stabilization of enzymes. 作为酶热稳定工具的非典型氨基酸。

IF 2.6 4区生物学

Protein Engineering Design & Selection Pub Date : 2023-01-21 DOI: 10.1093/protein/gzad003

Tim Lugtenburg, Alejandro Gran-Scheuch, Ivana Drienovská

引用次数: 0