Protein Engineering Design & Selection最新文献_第8页

DE-STRESS: a user-friendly web application for the evaluation of protein designs. DE-STRESS：用于评估蛋白质设计的用户友好型网络应用程序。

IF 2.6 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab029

Michael J Stam, Christopher W Wood

{"title":"DE-STRESS: a user-friendly web application for the evaluation of protein designs.","authors":"Michael J Stam, Christopher W Wood","doi":"10.1093/protein/gzab029","DOIUrl":"10.1093/protein/gzab029","url":null,"abstract":"De novo protein design is a rapidly growing field, and there are now many interesting and useful examples of designed proteins in the literature. However, most designs could be classed as failures when characterised in the lab, usually as a result of low expression, misfolding, aggregation or lack of function. This high attrition rate makes protein design unreliable and costly. It is possible that some of these failures could be caught earlier in the design process if it were quick and easy to generate information and a set of high-quality metrics regarding designs, which could be used to make reproducible and data-driven decisions about which designs to characterise experimentally. We present DE-STRESS (DEsigned STRucture Evaluation ServiceS), a web application for evaluating structural models of designed and engineered proteins. DE-STRESS has been designed to be simple, intuitive to use and responsive. It provides a wealth of information regarding designs, as well as tools to help contextualise the results and formally describe the properties that a design requires to be fit for purpose.","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39814973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Exploring the binding of rationally engineered tandem-repeat proteins to E3 ubiquitin ligase Keap1. 探索合理设计的串联重复蛋白与 E3 泛素连接酶 Keap1 的结合。

IF 2.6 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab027

Sarah K Madden, Laura S Itzhaki

引用次数: 0

Recent developments in engineering protein-protein interactions using phage display. 利用噬菌体展示技术工程蛋白-蛋白相互作用的最新进展。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab014

Chen T Liang, Olivia M A Roscow, Wei Zhang

引用次数: 5

Improvement of Moloney murine leukemia virus reverse transcriptase thermostability by introducing a disulfide bridge in the ribonuclease H region. 在核糖核酸酶H区引入二硫桥改善Moloney小鼠白血病病毒逆转录酶的热稳定性。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab006

Yutaro Narukawa, Mako Kandabashi, Tongyang Li, Misato Baba, Haruka Hara, Kenji Kojima, Kei Iida, Takayoshi Hiyama, Sho Yokoe, Tomomi Yamazaki, Teisuke Takita, Kiyoshi Yasukawa

引用次数: 2

The design and evolution of fluorescent protein-based sensors for monoatomic ions in biology. 生物学中基于荧光蛋白的单原子离子传感器的设计与发展。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab023

Kiheon Baek, Ke Ji, Weicheng Peng, Sureshee M Liyanaarachchi, Sheel C Dodani

{"title":"The design and evolution of fluorescent protein-based sensors for monoatomic ions in biology.","authors":"Kiheon Baek, Ke Ji, Weicheng Peng, Sureshee M Liyanaarachchi, Sheel C Dodani","doi":"10.1093/protein/gzab023","DOIUrl":"10.1093/protein/gzab023","url":null,"abstract":"Living cells rely on a finely tuned symphony of inorganic ion gradients composed of both cations and anions. This delicate balance is maintained by biological receptors all acting in concert to selectively recognize and position ions for homeostasis. These dynamic processes can be intercepted and visualized with optical microscopy at the organismal, tissue, cellular and subcellular levels using fluorescent protein-based biosensors. Since the first report of such tool for calcium (Ca2+) in 1997, outstanding biological questions and innovations in protein engineering along with associated fields have driven the development of new biosensors for Ca2+ and beyond. In this Review, we summarize a workflow that can be used to generate fluorescent protein-based biosensors to study monoatomic ions in biology. To showcase the scope of this approach, we highlight recent advances reported for Ca2+ biosensors and in detail discuss representative case studies of biosensors reported in the last four years for potassium (K+), magnesium (Mg2+), copper (Cu2+/+), lanthanide (Ln3+) and chloride (Cl-) ions.","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477612/pdf/gzab023.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39467110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 6

The evolution and engineering of enzyme activity through tuning conformational landscapes. 通过调整构象景观的酶活性的进化和工程。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab009

Adam M Damry, Colin J Jackson

引用次数: 7

Extended yeast surface display linkers enhance the enrichment of ligands in direct mammalian cell selections. 在哺乳动物细胞的直接选择中，扩展的酵母表面显示连接体增强了配体的富集。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab004

Patrick S Lown, Jessy J Cai, Seth C Ritter, Jacob J Otolski, Ryan Wong, Benjamin J Hackel

{"title":"Extended yeast surface display linkers enhance the enrichment of ligands in direct mammalian cell selections.","authors":"Patrick S Lown, Jessy J Cai, Seth C Ritter, Jacob J Otolski, Ryan Wong, Benjamin J Hackel","doi":"10.1093/protein/gzab004","DOIUrl":"10.1093/protein/gzab004","url":null,"abstract":"Selections of yeast-displayed ligands on mammalian cell monolayers benefit from high target expression and nanomolar affinity, which are not always available. Prior work extending the yeast-protein linker from 40 to 80 amino acids improved yield and enrichment but is hypothesized to be below the optimal length, prompting evaluation of an extended amino acid linker. A 641-residue linker provided enhanced enrichment with a 2-nM affinity fibronectin ligand and 105 epidermal growth factor receptors (EGFR) per cell (14 ± 2 vs. 8 ± 1, P = 0.008) and a >600-nM affinity ligand, 106 EGFR per cell system (23 ± 7 vs. 0.8 ± 0.2, P = 0.004). Enhanced enrichment was also observed with a 310-nM affinity affibody ligand and 104 CD276 per cell, suggesting a generalizable benefit to other scaffolds and targets. Spatial modeling of the linker suggests that improved extracellular accessibility of ligand enables the observed enrichment under conditions not previously possible.","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058008/pdf/gzab004.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38893447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 2

Evolution of β-lactamases and enzyme promiscuity. β-内酰胺酶的进化与酶的混杂性。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab013

Christopher Fröhlich, John Z Chen, Sevan Gholipour, Ayse N Erdogan, Nobuhiko Tokuriki

引用次数: 11

Protein engineering for natural product biosynthesis and synthetic biology applications. 用于天然产物生物合成和合成生物学应用的蛋白质工程。

IF 2.6 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab015

Miles A Calzini, Alexandra A Malico, Melissa M Mitchler, Gavin J Williams

引用次数: 0

Generation of a nanobody against HER2 tyrosine kinase using phage display library screening for HER2-positive breast cancer therapy development. 利用噬菌体展示文库筛选抗HER2酪氨酸激酶纳米体用于HER2阳性乳腺癌治疗开发

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab030

Thomanai Lamtha, Lueacha Tabtimmai, Kunan Bangphoomi, Duangnapa Kiriwan, Aijaz A Malik, Wanpen Chaicumpa, Paul M P van Bergen En Henegouwen, Kiattawee Choowongkomon

{"title":"Generation of a nanobody against HER2 tyrosine kinase using phage display library screening for HER2-positive breast cancer therapy development.","authors":"Thomanai Lamtha, Lueacha Tabtimmai, Kunan Bangphoomi, Duangnapa Kiriwan, Aijaz A Malik, Wanpen Chaicumpa, Paul M P van Bergen En Henegouwen, Kiattawee Choowongkomon","doi":"10.1093/protein/gzab030","DOIUrl":"https://doi.org/10.1093/protein/gzab030","url":null,"abstract":"Human epidermal growth factor receptor 2 (HER2) protein overexpression is found in ~30% of invasive breast carcinomas and in a high proportion of noninvasive ductal carcinomas in situ. Targeted cancer therapy is based on monoclonal antibodies and kinase inhibitors and reflects a new era of cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. Furthermore, there are many disadvantages with the current anti-HER2 drug, including drug resistance and adverse effects. Nanobodies (15 kDa), single-domain antibody (sdAb) fragments, can overcome these limitations. This study produced the recombinant sdAb against the HER2-tyrosine kinase (HER2-TK) domain using phage display technology. Three specific anti-HER2-TK sdAbs were selected for further characterization. Hallmark VHH residue identification and amino acid sequence analysis revealed that clone numbers 4 and 22 were VH antibodies, whereas clone number 17 was a VH H antibody (nanobody). The half-maximal inhibitory concentration of VHH17 exhibited significantly greater HER2 kinase-inhibition activity than the other clones. Consistent with these results, several charges and polar residues of the HER2-TK activation loop that were predicted based on mimotope analysis also appeared in the docking result and interacted via the CDR1, CDR2 and CDR3 loops of VHH17. Furthermore, the cell-penetrable VHH17 (R9 VHH17) showed cell-penetrability and significantly decreased HER2-positive cancer cell viability. Thus, the VH H17 could be developed as an effective therapeutic agent to treat HER2-positive breast cancer.","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39814974","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: 6