Related Experiment Video
Updated: Dec 15, 2025

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach
Published on: February 21, 2019
Multi-substrate selectivity based on key loops and non-homologous domains: new insight into ALKBH family
Baofang Xu1, Dongyang Liu1,2,3, Zerong Wang1
1The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, 010070, China.
Abstract:
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.
More Related Videos
Related Concept Videos
Allosteric Proteins-ATCase
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Ligand Binding and Linkage
Cooperative Allosteric Transitions
Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
Allosteric Regulation
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...

