5nc8

Publication Abstract from PubMed

Ligand binding is one of the most fundamental properties of proteins. Ligand functions fall into three basic types: substrates, regulatory molecules, and cofactors essential to protein stability, reactivity, or enzyme-substrate complex formation. The regulation of potassium ion movement in bacteria is predominantly under the control of regulatory ligands that gate the relevant channels and transporters, which possess subunits or domains that contain Rossmann folds (RFs). Here we demonstrate that adenosine monophosphate (AMP) is bound to both RFs of the dimeric bacterial Kef potassium efflux system (Kef), where it plays a structural role. We conclude that AMP binds with high affinity, ensuring that the site is fully occupied at all times in the cell. Loss of the ability to bind AMP, we demonstrate, causes protein, and likely dimer, instability and consequent loss of function. Kef system function is regulated via the reversible binding of comparatively low-affinity glutathione-based ligands at the interface between the dimer subunits. We propose this interfacial binding site is itself stabilized, at least in part, by AMP binding.

Adenosine Monophosphate Binding Stabilizes the KTN Domain of the Shewanella denitrificans Kef Potassium Efflux System.,Pliotas C, Grayer SC, Ekkerman S, Chan AKN, Healy J, Marius P, Bartlett W, Khan A, Cortopassi WA, Chandler SA, Rasmussen T, Benesch JLP, Paton RS, Claridge TDW, Miller S, Booth IR, Naismith JH, Conway SJ Biochemistry. 2017 Aug 15;56(32):4219-4234. doi: 10.1021/acs.biochem.7b00300., Epub 2017 Aug 4. PMID:28656748^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.