The Molecular Basis of Human ALKBH3 Mediated RNA N1-methyladenosine (m1A) Demethylation,Angewandte Chemie International Edition

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The Molecular Basis of Human ALKBH3 Mediated RNA N1-methyladenosine (m1A) Demethylation
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2023-12-29 , DOI: 10.1002/anie.202313900
Lin Zhang ₁ , Hong-Chao Duan ₂ , Marcin Paduch ₃ , Jingyan Hu ₁ , Chi Zhang ₂ , Yajuan Mu ₁ , Houwen Lin _{4,

5} , Chuan He _{6,

7,

8} , Anthony A Kossiakoff _{3,

8} , Guifang Jia _{2,

9} , Liang Zhang ₁

Affiliation

Department of Pharmacology and Chemical Biology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA.
Research Centre for Marine Drugs, State Key Laboratory of Oncogene and Related Genes, Department of Pharmacy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Institute of Marine Biomedicine, Shenzhen Polytechnic, Shenzhen, 518055, China.
Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA.
Howard Hughes Medical Institute, University of Chicago, Chicago, IL, USA.
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.
Peking-Tsinghua Center for Life Sciences, Beijing, 100871, China.

The distinct RNA m¹A substrate recognition and demethylation catalytic mechanisms of ALKBH3 were reported. It utilized a non-conserved β-hairpin as well as two bubble regions inside the active pocket generated by two key residues Asp194 and Thr133 to achieve single stranded substrates preferential recognition and demethylation catalysis.

中文翻译：

人 ALKBH3 介导的 RNA N1-甲基腺苷 (m1A) 去甲基化的分子基础

报道了 ALKBH3 独特的 RNA m ¹ A 底物识别和去甲基化催化机制。它利用非保守的β-发夹以及两个关键残基Asp194和Thr133产生的活性口袋内的两个气泡区域来实现单链底物的优先识别和去甲基化催化。

更新日期：2023-12-29

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