Polyamine acetylation and substrate-induced oligomeric states in histone acetyltransferase of multiple drug resistant Acinetobacter baumannii
| Autor: | Jyoti Singh Tomar, Ramakrishna V. Hosur |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Acinetobacter baumannii
0301 basic medicine Spermidine Spermine Biochemistry 03 medical and health sciences chemistry.chemical_compound Kanamycin Drug Resistance Multiple Bacterial Escherichia coli Polyamines Histone Acetyltransferases 030102 biochemistry & molecular biology biology Acetylation General Medicine Histone acetyltransferase 030104 developmental biology Histone chemistry Biofilms Acetyltransferase biology.protein Polyamine acetylation Protein Multimerization Polyamine |
| Zdroj: | Biochimie. 168:268-276 |
| ISSN: | 0300-9084 |
| DOI: | 10.1016/j.biochi.2019.11.015 |
| Popis: | Histone acetyltransferase (Hpa2) is an unusual acetyltransferase, with a wide range of substrates; including histones, polyamines and aminoglycosides antibiotic. Hpa2 belongs to GNAT superfamily and GNATs are well known for the formation of homo-oligomers. However, the reason behind their oligomerization remained unexplored. Here, oligomeric states of Hpa2 were explored, to understand the functional significance of oligomerization. Biochemical analysis suggests that Hpa2 exists as dimer in solution and self-assembles into tetramer in the spermine, spermidine and kanamycin bound form. Stability analysis with denaturants concludes that homo-oligomerization of Hpa2 relies on bound substrate and not on experimental conditions. Homo-oligomerization in Hpa2 depicts direct correlation with its polyamine acetylating capacity. This correlation and in silico model structures suggest that oligomerization of Hpa2 is associated with the hastening of acetylation process. Interestingly, polyamine acetylation down regulates biofilms formation in E. coli BL21/Hpa2-transformants cells. Therefore, we propose that Hpa2 manipulates survival strategies of the bacterium via polyamines and antibiotics acetylation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect