Structural analysis of a shrimp thymidylate synthase reveals species-specific interactions with dUMP and raltitrexed
文献类型：CNKI期刊论文
| 作者 | LIU Changshui; ZANG Kun; LI Shihao; LI Fuhua; MA Qingjun |
| 发表日期 | 2020-11-15 |
| 出处 | Journal of Oceanology and Limnology
 |
| 关键词 | thymidylate synthase (TS) closed conformation deoxyuridine monophosphate (dUMP) thymidine monophosphate(TMP) raltitrexed Litopenaeus vannamei |
| 英文摘要 | Thymidylate synthase(TS) is a key enzyme in the de novo biosynthesis of thymidine monophosphate,serving as a well-known drug target in chemotherapy against cancers and infectious diseases.Additional to its clinical value,TS is supposed to be a promising drug target in aquatic-disease control.To facilitate designing pathogen-specific TS inhibitors for shrimp-disease control,we report the crystal structures of TS from Litopenaeus vannamei(LvTS) in the apo form,LvTS-dUMP complex and LvTS-dUMP-raltitrexed complex at 2.27 ?,1.54 ?,and 1.56 A resolution,respectively.LvTS shares a similar fold with known TSs,existing as a dimer in the crystal.The apo LvTS and LvTS-dUMP take an open conformation,and raltitrexed binding induces structural changes into a closed conformation in LvTSdUMP-raltitrexed.Compared to those in other known TS-dUMP-raltitrexed complexes with the closed conformation,the C-terminal loop in LvTS-dUMP-raltitrexed shifts its position away from the bound raltitrexed;the distance between C6 of dUMP and Sy of the catalytic cysteine is obviously longer than that in the known TS structures with closed conformations,resembling that in the TS structures with open conformations.Other species-specific interactions with dUMP and raltitrexed are also observed.Therefore,LvT S-dUMP-raltitrexed adopts a loosely dosed conformation with structural features inte rmediate between the closed and the open conformations that were reported in other TSs.Our study provides the first crustcean TS structure,and reveals species-specific interactions between TSs and the ligands,which would facilitate designing pathogen-specific TS inhibitors for shrimp-disease control. |
| 文献子类 | CNKI期刊论文 |
| 资助机构 | Supported by the National Natural Science Foundation of China (Nos. 31572660,31872600) ; the “1000 Talents Program” ; the Qingdao Innovation Leadership Project (No. 18-1-2-12-zhc) |
| 卷 | v.38期:06页:295-303 |
| 语种 | 英文; |
| 分类号 | S943 |
| ISSN号 | 2096-5508 |
| 源URL | [http://ir.qdio.ac.cn/handle/337002/187959]  |
| 专题 | 中国科学院海洋研究所 |
| 作者单位 | 1.KeyLaboratoryofExperimentalMarineBiology,InstituteofOceanology,ChineseAcademyofSciences 2.LaboratoryforMarineBiologyandBiotechnology,QingdaoNationalLaboratoryforMarineScienceandTechnology 3.UniversityofChineseAcademyofSciences 4.CenterforOceanMega-Science,ChineseAcademyofSciences |
| 推荐引用方式 GB/T 7714 | LIU Changshui,ZANG Kun,LI Shihao,et al. Structural analysis of a shrimp thymidylate synthase reveals species-specific interactions with dUMP and raltitrexed. 2020. |
入库方式： OAI收割
来源：海洋研究所
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