Computational characterization of substrate and product specificities, and functionality of S-adenosylmethionine binding pocket in histone lysine methyltransferases from Arabidopsis, rice and maize
| Autor: | Eerappa Rajakumara, Madishetti Vinuthna Vani, Dixit Shivani, Mutyala Satish, Suman Abhishek, Naveen Kumar Nakarakanti, M. Angel Nivya |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
S-Adenosylmethionine Methyltransferase Histone lysine methylation Protein Conformation Arabidopsis Biochemistry Histone-Lysine N-Methyltransferase Methylation Zea mays Catalysis Substrate Specificity Histones 03 medical and health sciences Histone H3 Structural Biology Sequence Analysis Protein Humans Databases Protein Molecular Biology Plant Proteins Binding Sites biology Molecular Structure Lysine EZH2 Oryza biology.organism_classification 030104 developmental biology Histone Models Chemical biology.protein Protein Processing Post-Translational Protein Binding |
| Zdroj: | Proteins. 86(1) |
| ISSN: | 1097-0134 |
| Popis: | Histone lysine methylation by histone lysine methyltransferases (HKMTs) has been implicated in regulation of gene expression. While significant progress has been made to understand the roles and mechanisms of animal HKMT functions, only a few plant HKMTs are functionally characterized. To unravel histone substrate specificity, degree of methylation and catalytic activity, we analyzed Arabidopsis Trithorax-like protein (ATX), Su(var)3-9 homologs protein (SUVH), Su(var)3-9 related protein (SUVR), ATXR5, ATXR6, and E(Z) HKMTs of Arabidopsis, maize and rice through sequence and structure comparison. We show that ATXs may exhibit methyltransferase specificity toward histone 3 lysine 4 (H3K4) and might catalyse the trimethylation. Our analyses also indicate that most SUVH proteins of Arabidopsis may bind histone H3 lysine 9 (H3K9). We also predict that SUVH7, SUVH8, SUVR1, SUVR3, ZmSET20 and ZmSET22 catalyse monomethylation or dimethylation of H3K9. Except for SDG728, which may trimethylate H3K9, all SUVH paralogs in rice may catalyse monomethylation or dimethylation. ZmSET11, ZmSET31, SDG713, SDG715, and SDG726 proteins are predicted to be catalytically inactive because of an incomplete S-adenosylmethionine (SAM) binding pocket and a post-SET domain. E(Z) homologs can trimethylate H3K27 substrate, which is similar to the Enhancer of Zeste homolog 2 of humans. Our comparative sequence analyses reveal that ATXR5 and ATXR6 lack motifs/domains required for protein-protein interaction and polycomb repressive complex 2 complex formation. We propose that subtle variations of key residues at substrate or SAM binding pocket, around the catalytic pocket, or presence of pre-SET and post-SET domains in HKMTs of the aforementioned plant species lead to variations in class-specific HKMT functions and further determine their substrate specificity, the degree of methylation and catalytic activity. |
| Databáze: | OpenAIRE |
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