Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.13.3 (histidine kinase)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The NifL regulatory protein is an anti-activator that tightly regulates transcription of genes required for nitrogen fixation in Azotobacter vinelandii by controlling the activity of its partner protein NifA through the formation of a protein-protein complex. NifL modulates the activity of NifA in response to the redox, carbon and nitrogen status to ensure that nitrogen fixation occurs only under physiological conditions that are appropriate for nitrogenase activity. The domain architecture of NifL is similar to that of some histidine protein kinases, with two N-terminal PAS (PER, ARNT, SIM) domains, one of which contains an FAD cofactor that senses the redox status, and a C-terminal domain containing conserved residues that constitutes the nucleotide-binding domain of the GHKL (gyrase, Hsp90, histidine kinase, MutL) superfamily of ATPases. We have evidence that the central region of NifL, which is located between the PAS domains and the C-terminal GHKL nucleotide-binding domain, plays a crucial role in the propagation of signals perceived in response to the redox and fixed nitrogen status and that this region participates in conformational changes that switch NifL between active and inactive states. We have identified a critical arginine residue in the central region of NifL that participates in the conformational switch that activates NifL. Mutations in the central region of NifL that disable the redox-sensing function of NifL but leave the protein competent to respond to the nitrogen signal conveyed by the signal transduction protein GlnK have also been isolated. Our results suggest that the topological relationship between the central region and the GHKL domain may alter as a consequence of conformational changes induced in response to signal perception.
 ...
PMID:Role of the central region of NifL in conformational switches that regulate nitrogen fixation. 1641 11

The cyanobacterium Synechocystis sp. PCC 6803 harbours 47 histidine kinases (Hiks). Among these are hybrid histidine kinases with one or two response regulator domains as well as numerous Hiks with several sensory domains. One example is the hybrid histidine kinase Slr1759 (Hik14) that has two PAS domains arranged in tandem linked to a predicted GAF domain. Here, we show that a Slr1759 derivative recombinantly expressed in Escherichia coli has a flavin cofactor. Using truncated Slr1759 variants, it is shown that the flavin associates with the first PAS domain. The cofactor reconstitutes the activity of D: -amino acid oxidase apoprotein from pig kidney, indicating that the flavin derivative is FAD. Furthermore, the Slr1759 histidine kinase domain indeed undergoes autophosphorylation in vitro. The phosphorylated product of a recombinant Slr1759 derivative is sensitive to acids, pointing to a histidine residue as the phosphate-accepting group.
 ...
PMID:The hybrid histidine kinase Slr1759 of the cyanobacterium Synechocystis sp. PCC 6803 contains FAD at its PAS domain. 1942 79