Journal article
Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus
Ian Monk, Nausad Shaikh, Stephanie Begg, Mike Gajdiss, Jean Lee, Sacha Pidot, Torsten Seemann, Michael Kuiper, Brit Winnen, Rikki Hvorup, Brett Collins, Gabriele Bierbaum, Benjamin Howden, Christopher McDevitt, Glenn King, Timothy Stinear
Published : 2018
DOI: 10.1101/405365
Abstract
ABSTRACT WalKR (YycFG) is the only essential two-component regulator in the human pathogen Staphylococcus aureus. WalKR regulates peptidoglycan synthesis, but this function alone appears not to explain its essentiality. To understand WalKR function we investigated a suppressor mutant that arose when WalKR activity was impaired; a single histidine to tryptophan substitution (H271Y) in the cytoplasmic Per-Arnt-Sim (PAS CYT ) domain of the histidine kinase WalK. Introduction of the WalK H271Y mutation into wild-type S . aureus activated the WalKR regulon. Structural analyses of the WalK PAS CYT domain revealed a hitherto unknown metal binding site, in which a zinc ion (Zn 2+ ) was tetrahedrally..
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