The structural basis for cancer drug interactions with the catalytic and allosteric sites of SAMHD1

Author:

Knecht Kirsten M.1,Buzovetsky Olga1,Schneider Constanze2,Thomas Dominique34,Srikanth Vishok1,Kaderali Lars5,Tofoleanu Florentina67,Reiss Krystle6,Ferreirós Nerea34,Geisslinger Gerd348,Batista Victor S.6ORCID,Ji Xiaoyun9,Cinatl Jindrich2,Keppler Oliver T.10,Xiong Yong1

Affiliation:

1. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520;

2. Institute of Medical Virology, University Hospital Frankfurt, 60596 Frankfurt, Germany;

3. Institute of Clinical Pharmacology, Pharmazentrum Frankfurt, Goethe University of Frankfurt, 60590 Frankfurt, Germany;

4. Zentrum für Arzneimittelforschung, -entwicklung, und -sicherheit, Goethe University of Frankfurt, 60590 Frankfurt, Germany;

5. Institute of Bioinformatics, University Medicine Greifswald, 17475 Greifswald, Germany;

6. Department of Chemistry, Yale University, New Haven, CT 06520;

7. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892;

8. Project Group Translational Medicine and Pharmacology, Frauenhofer Institute for Molecular Biology and Applied Ecology, 60590 Frankfurt, Germany;

9. The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023 Jiangsu, China;

10. Max von Pettenkofer-Institute, Department of Virology, Ludwig Maximilians University, 80336 Munich, Germany

Abstract

Significance Nucleoside analog drugs are widely used to treat a variety of cancers and viral infections. With an essential role in regulating the nucleotide pool in the cell by degrading cellular nucleotides, SAMHD1 has the potential to decrease the cellular concentration of frequently prescribed nucleoside analogs and thereby decrease their clinical efficacy in cancer therapy. To improve future nucleoside analog treatments, it is important to understand SAMHD1 interactions with these drugs. Our work thoroughly examines the extent to which nucleotide analogs interact with the catalytic and allosteric sites of SAMHD1. This work contributes to the assessment of SAMHD1 as a potential therapeutic target for cancer therapy and the future design of SAMHD1 modulators that might improve the efficacy of existing therapies.

Publisher

Proceedings of the National Academy of Sciences

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.7亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2025 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3