Journal
BIOCHEMICAL SOCIETY TRANSACTIONS
Volume 39, Issue -, Pages 647-651Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BST0390647
Keywords
bis-(3 '-5 '-cyclic dimeric GMP (c-di-GMP); guanine; ligand binding; riboswitch; signalling
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Funding
- NIGMS NIH HHS [P01 GM022778, GM022778] Funding Source: Medline
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The c-di-GMP [bis-(3'-5')-cyclic dimeric guanosine monophosphate] riboswitch is a macromolecular target in the c-di-GMP second messenger signalling pathway. It regulates many genes related to c-di-GMP metabolism as well as genes involved in bacterial motility, virulence and biofilm formation. The riboswitch makes asymmetric contacts to the bases and phosphate backbone of this symmetric dinucleotide. The phylogenetics suggested and mutagenesis has confirmed that this is a flexible motif where variants can make alternative interactions with each of the guanine bases of c-di-GMP. A mutant riboswitch has been designed that can bind a related molecule, c-di-AMP, confirming the most important contacts made to the ligand. The binding kinetics reveal that this is a kinetically controlled riboswitch and mutations to the riboswitch lead to increases in the off-rate. This riboswitch is therefore flexible in sequence as well as kinetic properties.
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