Multi-substrate selectivity based on key loops and non-homologous domains: new insight into ALKBH family
| Autor: | Zerong Wang, Baofang Xu, Ruixia Tian, Dongyang Liu, Yongchun Zuo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Pharmacology
0303 health sciences Phylogenetic tree AlkB Enzymes biology Chemistry 030302 biochemistry & molecular biology Cell Biology Computational biology 03 medical and health sciences Cellular and Molecular Neuroscience Transfer RNA Molecular mechanism Homologous chromosome biology.protein Molecular Medicine Demethylase Selectivity Molecular Biology Demethylation |
| Zdroj: | Cellular and Molecular Life Sciences. 78:129-141 |
| ISSN: | 1420-9071 1420-682X |
| DOI: | 10.1007/s00018-020-03594-9 |
| Popis: | AlkB homologs (ALKBH) are a family of specific demethylases that depend on Fe2+ and α-ketoglutarate to catalyze demethylation on different substrates, including ssDNA, dsDNA, mRNA, tRNA, and proteins. Previous studies have made great progress in determining the sequence, structure, and molecular mechanism of the ALKBH family. Here, we first review the multi-substrate selectivity of the ALKBH demethylase family from the perspective of sequence and structural evolution. The construction of the phylogenetic tree and the comparison of key loops and non-homologous domains indicate that the paralogs with close evolutionary relationship have similar domain compositions. The structures show that the lack and variations of four key loops change the shape of clefts to cause the differences in substrate affinity, and non-homologous domains may be related to the compatibility of multiple substrates. We anticipate that the new insights into selectivity determinants of the ALKBH family are useful for understanding the demethylation mechanisms. |
| Databáze: | OpenAIRE |
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