Understanding ATP Binding to DosS Catalytic Domain with a Short ATP-Lid.

ABSTRACT: DosS is a heme-containing histidine kinase that triggers dormancy transformation inMycobacterium tuberculosis. Sequence comparison of the catalytic ATP-binding (CA) domain of DosS to other well-studied histidine kinases reveals a short ATP-lid. This feature has been thought to block binding of ATP to DosS's CA domain in the absence of interactions with DosS's dimerization and histidine phospho-transfer (DHp) domain. Here, we use a combination of computational modeling, structural biology, and biophysical studies to re-examine ATP-binding modalities in DosS. We show that the closed-lid conformation observed in crystal structures of DosS CA is caused by the presence of Zn²⁺ in the ATP binding pocket that coordinates with Glu537 on the ATP-lid. Furthermore, circular dichrois

SUBMITTER: Larson GW 

PROVIDER: S-EPMC11152246 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature