Enzymes最新文献_第10页

Structures and functions of multi-tRNA synthetase complexes. 多trna合成酶复合物的结构和功能。

Enzymes Pub Date : 2020-01-01 Epub Date: 2020-09-08 DOI: 10.1016/bs.enz.2020.06.008

Myung Hee Kim, Sunghoon Kim

引用次数: 6

Aminoacyl-tRNA synthetases as drug targets. 氨基酰基- trna合成酶作为药物靶点。

Enzymes Pub Date : 2020-01-01 Epub Date: 2020-10-14 DOI: 10.1016/bs.enz.2020.07.001

Maria Lukarska, Andrés Palencia

{"title":"Aminoacyl-tRNA synthetases as drug targets.","authors":"Maria Lukarska, Andrés Palencia","doi":"10.1016/bs.enz.2020.07.001","DOIUrl":"https://doi.org/10.1016/bs.enz.2020.07.001","url":null,"abstract":"Aminoacyl-tRNA synthetases (AARSs) have been considered very attractive drug-targets for decades. This interest probably emerged with the identification of differences in AARSs between prokaryotic and eukaryotic species, which provided a rationale for the development of antimicrobials targeting bacterial AARSs with minimal effect on the homologous human AARSs. Today we know that AARSs are not only attractive, but also valid drug targets as they are housekeeping proteins that: (i) play a fundamental role in protein translation by charging the corresponding amino acid to its cognate tRNA and preventing mistranslation mistakes [1], a critical process during fast growing conditions of microbes; and (ii) present significant differences between microbes and humans that can be used for drug development [2]. Together with the vast amount of available data on both pathogenic and mammalian AARSs, it is expected that, in the future, the numerous reported inhibitors of AARSs will provide the basis to develop new therapeutics for the treatment of human diseases. In this chapter, a detailed summary on the state-of-the-art in drug discovery and drug development for each aminoacyl-tRNA synthetase will be presented.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"48 ","pages":"321-350"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.enz.2020.07.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25593404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Overview of flavin-dependent enzymes. 黄素依赖酶综述。

Enzymes Pub Date : 2020-01-01 Epub Date: 2020-08-21 DOI: 10.1016/bs.enz.2020.06.006

Panu Pimviriyakul, Pimchai Chaiyen

引用次数: 4

Phenolic hydroxylases. 酚羟化酶。

Enzymes Pub Date : 2020-01-01 Epub Date: 2020-07-18 DOI: 10.1016/bs.enz.2020.05.008

Pirom Chenprakhon, Panu Pimviriyakul, Chanakan Tongsook, Pimchai Chaiyen

{"title":"Phenolic hydroxylases.","authors":"Pirom Chenprakhon, Panu Pimviriyakul, Chanakan Tongsook, Pimchai Chaiyen","doi":"10.1016/bs.enz.2020.05.008","DOIUrl":"https://doi.org/10.1016/bs.enz.2020.05.008","url":null,"abstract":"Many flavin-dependent phenolic hydroxylases (monooxygenases) have been extensively investigated. Their crystal structures and reaction mechanisms are well understood. These enzymes belong to groups A and D of the flavin-dependent monooxygenases and can be classified as single-component and two-component flavin-dependent monooxygenases. The insertion of molecular oxygen into the substrates catalyzed by these enzymes is beneficial for modifying the biological properties of phenolic compounds and their derivatives. This chapter provides an in-depth discussion of the structural features of single-component and two-component flavin-dependent phenolic hydroxylases. The reaction mechanisms of selected enzymes, including 3-hydroxy-benzoate 4-hydroxylase (PHBH) and 3-hydroxy-benzoate 6-hydroxylase as representatives of single-component enzymes and 3-hydroxyphenylacetate 4-hydroxylase (HPAH) as a representative of two-component enzymes, are discussed in detail. This chapter comprises the following four main parts: general reaction, structures, reaction mechanisms, and enzyme engineering for biocatalytic applications. Enzymes belonging to the same group catalyze similar reactions but have different unique structural features to control their reactivity to substrates and the formation and stabilization of C4a-hydroperoxyflavin. Protein engineering has been employed to improve the ability to use these enzymes to synthesize valuable compounds. A thorough understanding of the structural and mechanistic features controlling enzyme reactivity is useful for enzyme redesign and enzyme engineering for future biocatalytic applications.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"47 ","pages":"283-326"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.enz.2020.05.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38401148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

The multipurpose family of flavoprotein oxidases. 多用途的黄蛋白氧化酶家族。

Enzymes Pub Date : 2020-01-01 Epub Date: 2020-07-18 DOI: 10.1016/bs.enz.2020.05.002

Caterina Martin, Claudia Binda, Marco W Fraaije, Andrea Mattevi

引用次数: 7

Vanillyl alcohol oxidase. 香草醇氧化酶。

Enzymes Pub Date : 2020-01-01 Epub Date: 2020-07-18 DOI: 10.1016/bs.enz.2020.05.003

Tom A Ewing, Gudrun Gygli, Marco W Fraaije, Willem J H van Berkel

引用次数: 11

Putting amino acids onto tRNAs: The aminoacyl-tRNA synthetases as catalysts. 把氨基酸放到trna上:氨酰基- trna合成酶作为催化剂。

Enzymes Pub Date : 2020-01-01 Epub Date: 2020-09-08 DOI: 10.1016/bs.enz.2020.06.003

Rebecca W Alexander, Tamara L Hendrickson

引用次数: 0

Porcine kidney d-amino acid oxidase-derived R-amine oxidases with new substrate specificities. 具有新底物特异性的猪肾d-氨基酸氧化酶衍生的r -胺氧化酶。

Enzymes Pub Date : 2020-01-01 Epub Date: 2020-08-05 DOI: 10.1016/bs.enz.2020.06.007

Kazuyuki Yasukawa, Nobuhiro Kawahara, Fumihiro Motojima, Shogo Nakano, Yasuhisa Asano

{"title":"Porcine kidney d-amino acid oxidase-derived R-amine oxidases with new substrate specificities.","authors":"Kazuyuki Yasukawa, Nobuhiro Kawahara, Fumihiro Motojima, Shogo Nakano, Yasuhisa Asano","doi":"10.1016/bs.enz.2020.06.007","DOIUrl":"https://doi.org/10.1016/bs.enz.2020.06.007","url":null,"abstract":"An R-stereoselective amine oxidase and variants with markedly altered substrate specificity toward (R)-amines were generated from porcine d-amino acid oxidase (pkDAO), based on the X-ray crystallographic analysis of the wild-type enzyme. The new R-amine oxidase, a pkDAO variant (Y228L/R283G), acted on α-MBA and its derivatives, α-ethylbenzylamine, alkylamine, and cyclic secondary amines, totally losing the activities toward the original substrates, d-amino acids. The variant is enantiocomplementary to the flavin-type S-stereoselective amine oxidase variant from Aspergillus niger. Moreover, we solved the structure of pkDAO variants and successfully applied the obtained information to generate more variants through rational protein engineering, and used them in the synthesis of pharmaceutically attractive chiral compounds. The pkDAO variant Y228L/R283G and a variant I230A/R283G were used to synthesize (S)-amine and (R)-4-CBHA through deracemization, from racemic α-methylbenzylamine and benzhydrylamine, respectively, by selective oxidation of one of the enantiomers in the presence of a chemical reductant such as NaBH4. From a mechanistic point of view, we speculated that the imine intermediate, synthesized by oxidases or dehydrogenases, could be converted into primary α-aminonitrile by nucleophilic addition of cyanide in aqueous solutions. Nitriles and some unnatural amino acids were synthesized through a cascade reaction by oxidative cyanation reaction with the variant and a wide substrate specificity nitrilase.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"47 ","pages":"117-136"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.enz.2020.06.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38398061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Baeyer-Villiger monooxygenases: From protein engineering to biocatalytic applications. Baeyer-Villiger单加氧酶:从蛋白质工程到生物催化应用。

Enzymes Pub Date : 2020-01-01 Epub Date: 2020-07-18 DOI: 10.1016/bs.enz.2020.05.007

Sandy Schmidt, Uwe T Bornscheuer

{"title":"Baeyer-Villiger monooxygenases: From protein engineering to biocatalytic applications.","authors":"Sandy Schmidt, Uwe T Bornscheuer","doi":"10.1016/bs.enz.2020.05.007","DOIUrl":"https://doi.org/10.1016/bs.enz.2020.05.007","url":null,"abstract":"Biocatalytic processes are well established for the synthesis of high-value fine chemicals, especially for chiral pharmaceutical intermediates, by using natural or engineered enzymes. In contrast, examples for the enzymatic synthesis of bulk chemicals are still rare. Especially for the synthesis of polymer precursors such as ɛ-caprolactone, that is still produced under harsh conditions by using peracetic acid, Baeyer-Villiger monooxygenases (BVMOs) represent promising alternative catalysts that can perform the reaction under mild conditions. However, industrial production of this bulk chemical using a biocatalyst such as a BVMO has not been achieved yet due to a number of reasons. In this book chapter, we are emphasizing the versatility of BVMOs and their catalyzed reactions, and address several examples where protein engineering was applied in order to overcome several limitations associated to the use of BVMOs. Finally, we highlight several examples of BVMO applications, either in single enzyme transformations, or BVMOs involved in cascade reactions. By mainly focusing on recent developments and achievements in the field, we outline different concepts that were developed in order to pave the way for an industrial application of BVMOs.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"47 ","pages":"231-281"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.enz.2020.05.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38401147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Aminoacyl-tRNA synthetases in cell signaling. 细胞信号转导中的氨基酰基trna合成酶。

Enzymes Pub Date : 2020-01-01 Epub Date: 2020-06-12 DOI: 10.1016/bs.enz.2020.04.002

Peng Yao, Paul L Fox

{"title":"Aminoacyl-tRNA synthetases in cell signaling.","authors":"Peng Yao, Paul L Fox","doi":"10.1016/bs.enz.2020.04.002","DOIUrl":"https://doi.org/10.1016/bs.enz.2020.04.002","url":null,"abstract":"Aminoacyl-tRNA synthetases (ARSs) are a family of essential \"housekeeping\" enzymes ubiquitous in the three major domains of life. ARSs uniquely connect the essential minimal units of both major oligomer classes-the 3-nucleotide codons of oligonucleotides and the amino acids of proteins. They catalyze the esterification of amino acids to the 3'-end of cognate transfer RNAs (tRNAs) bearing the correct anticodon triplet to ensure accurate transfer of information from mRNA to protein according to the genetic code. As an essential translation factor responsible for the first biochemical reaction in protein biosynthesis, ARSs control protein production by catalyzing aminoacylation, and by editing of mischarged aminoacyl-tRNAs to maintain translational fidelity. In addition to their primary enzymatic activities, many ARSs have noncanonical functions unrelated to their catalytic activity in protein synthesis. Among the ARSs with \"moonlighting\" activities, several, including GluProRS (or EPRS), LeuRS, LysRS, SerRS, TyrRS, and TrpRS, exhibit cell signaling-related activities that sense environmental signals, regulate gene expression, and modulate cellular functions. ARS signaling functions generally depend on catalytically-inactive, appended domains not present in ancient enzyme forms, and are activated by stimulus-dependent post-translational modification. Activation often results in cellular re-localization and gain of new interacting partners. The newly formed ARS-bearing complexes conduct a host of signal transduction functions, including immune response, mTORC1 pathway signaling, and fibrogenic and angiogenic signaling, among others. Because noncanonical functions of ARSs in signal transduction are uncoupled from canonical aminoacylation functions, function-specific inhibitors can be developed, thus providing promising opportunities and therapeutic targets for treatment of human disease.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"48 ","pages":"243-275"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.enz.2020.04.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25576705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6