具有抗端粒酶活性的红红螺旋菌l-天冬酰胺酶突变体的理化性质

M. Pokrovskaya, S. Aleksandrova, A. Veselovsky, D. D. Zdanov, V. Pokrovsky, M. Eldarov, D. V. Grishin, Y. Gladilina, I.Yu. Toropigin, N. Sokolov
{"title":"具有抗端粒酶活性的红红螺旋菌l-天冬酰胺酶突变体的理化性质","authors":"M. Pokrovskaya, S. Aleksandrova, A. Veselovsky, D. D. Zdanov, V. Pokrovsky, M. Eldarov, D. V. Grishin, Y. Gladilina, I.Yu. Toropigin, N. Sokolov","doi":"10.18097/BMCRM00071","DOIUrl":null,"url":null,"abstract":"Rru_A3730 protein is a bacterial Rhodospirillum rubrum L-asparaginase (RrA), which is known by its anticancer activity. RrA variants with point amino acid substitutions in the region of 150 amino acids residues: RrA17N, K149E, RrAE149R, V150P, F151T, RrА17N, E149R, V150P, RrAE149R, V150P, showed antiproliferative properties, and also by their ability to suppress telomerase activity. This work is devoted to comparison of physical-chemical and catalytic properties of these mutant forms of RrA. It is shown that pH optimum is in the alkaline zone (8.5 – 9.3); L-glutaminase and D-asparaginase activity is respectively not more than 0.1% and 1.6% of L-asparaginase for all studied variants of RrA. The presence of the N17-terminal amino acid sequence MASMTGGQMGRGSSRQ of the capsid protein of bacteriophage T7 in the RrA structure leads to an increase in the thermal stability of mutant RrA analogues (from 50°C to 56°C) and their resistance to denaturation in the presence of 3 – 4 M urea. It is of Metal ions exhibit multidirectional effects on L-asparaginase activity of RrA. K+, Ca2+, Zn2+, Cs+, Co2+ in significantly affect the activity of L-asparaginase, while Mn2+, Cu2+, Fe3+ ions inhibit it. There was no correlation between antitelomerase (antiproliferative) activity and kinetic properties of mutant forms of L-asparaginase RrA.","PeriodicalId":286037,"journal":{"name":"Biomedical Chemistry: Research and Methods","volume":"70 5","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2019-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":"{\"title\":\"Physical-Chemical Properties of L-asparaginase Mutants From Rhodospirillum Rubrum which Showed Antitelomerase Activity\",\"authors\":\"M. Pokrovskaya, S. Aleksandrova, A. Veselovsky, D. D. Zdanov, V. Pokrovsky, M. Eldarov, D. V. Grishin, Y. Gladilina, I.Yu. Toropigin, N. Sokolov\",\"doi\":\"10.18097/BMCRM00071\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Rru_A3730 protein is a bacterial Rhodospirillum rubrum L-asparaginase (RrA), which is known by its anticancer activity. RrA variants with point amino acid substitutions in the region of 150 amino acids residues: RrA17N, K149E, RrAE149R, V150P, F151T, RrА17N, E149R, V150P, RrAE149R, V150P, showed antiproliferative properties, and also by their ability to suppress telomerase activity. This work is devoted to comparison of physical-chemical and catalytic properties of these mutant forms of RrA. It is shown that pH optimum is in the alkaline zone (8.5 – 9.3); L-glutaminase and D-asparaginase activity is respectively not more than 0.1% and 1.6% of L-asparaginase for all studied variants of RrA. The presence of the N17-terminal amino acid sequence MASMTGGQMGRGSSRQ of the capsid protein of bacteriophage T7 in the RrA structure leads to an increase in the thermal stability of mutant RrA analogues (from 50°C to 56°C) and their resistance to denaturation in the presence of 3 – 4 M urea. It is of Metal ions exhibit multidirectional effects on L-asparaginase activity of RrA. K+, Ca2+, Zn2+, Cs+, Co2+ in significantly affect the activity of L-asparaginase, while Mn2+, Cu2+, Fe3+ ions inhibit it. There was no correlation between antitelomerase (antiproliferative) activity and kinetic properties of mutant forms of L-asparaginase RrA.\",\"PeriodicalId\":286037,\"journal\":{\"name\":\"Biomedical Chemistry: Research and Methods\",\"volume\":\"70 5\",\"pages\":\"0\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2019-02-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedical Chemistry: Research and Methods\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.18097/BMCRM00071\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Chemistry: Research and Methods","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.18097/BMCRM00071","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3

摘要

Rru_A3730蛋白是一种细菌红红螺旋菌l -天冬酰胺酶(RrA),以其抗癌活性而闻名。RrA17N、K149E、RrAE149R、V150P、F151T、RrА17N、E149R、V150P、RrAE149R、V150P等在150个氨基酸残基区域具有点氨基酸取代的RrA变异体表现出抗增殖特性,同时也表现出抑制端粒酶活性的能力。这项工作致力于比较这些突变形式的RrA的物理化学和催化性能。结果表明,最佳pH值在碱性区(8.5 ~ 9.3);所有RrA变异株的l -谷氨酰胺酶和d -天冬酰胺酶活性分别不超过l -天冬酰胺酶的0.1%和1.6%。噬菌体T7衣壳蛋白n17端氨基酸序列MASMTGGQMGRGSSRQ在RrA结构中存在,导致突变体RrA类似物的热稳定性(从50°C增加到56°C)和在3 - 4 M尿素存在下的抗变性能力增加。金属离子对RrA的l -天冬酰胺酶活性具有多向影响。K+、Ca2+、Zn2+、Cs+、Co2+对l -天冬酰胺酶活性有显著影响,而Mn2+、Cu2+、Fe3+对l -天冬酰胺酶活性有抑制作用。抗端粒酶(抗增殖)活性与l -天冬酰胺酶RrA突变体的动力学特性无相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Physical-Chemical Properties of L-asparaginase Mutants From Rhodospirillum Rubrum which Showed Antitelomerase Activity
Rru_A3730 protein is a bacterial Rhodospirillum rubrum L-asparaginase (RrA), which is known by its anticancer activity. RrA variants with point amino acid substitutions in the region of 150 amino acids residues: RrA17N, K149E, RrAE149R, V150P, F151T, RrА17N, E149R, V150P, RrAE149R, V150P, showed antiproliferative properties, and also by their ability to suppress telomerase activity. This work is devoted to comparison of physical-chemical and catalytic properties of these mutant forms of RrA. It is shown that pH optimum is in the alkaline zone (8.5 – 9.3); L-glutaminase and D-asparaginase activity is respectively not more than 0.1% and 1.6% of L-asparaginase for all studied variants of RrA. The presence of the N17-terminal amino acid sequence MASMTGGQMGRGSSRQ of the capsid protein of bacteriophage T7 in the RrA structure leads to an increase in the thermal stability of mutant RrA analogues (from 50°C to 56°C) and their resistance to denaturation in the presence of 3 – 4 M urea. It is of Metal ions exhibit multidirectional effects on L-asparaginase activity of RrA. K+, Ca2+, Zn2+, Cs+, Co2+ in significantly affect the activity of L-asparaginase, while Mn2+, Cu2+, Fe3+ ions inhibit it. There was no correlation between antitelomerase (antiproliferative) activity and kinetic properties of mutant forms of L-asparaginase RrA.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信