3zxq

CRYSTAL STRUCTURE OF THE ATP-BINDING DOMAIN OF MYCOBACTERIUM TUBERCULOSIS DOSTCRYSTAL STRUCTURE OF THE ATP-BINDING DOMAIN OF MYCOBACTERIUM TUBERCULOSIS DOST

Structural highlights 3zxq is a 2 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DOST_MYCTU Interacts with the two-component regulatory system DevR/DevS (DosR/DosS) involved in onset of the dormancy response. May act as a direct hypoxia sensor (rather than a redox sensor); the normal state is the oxygenated form, while the deoxy form is probably active for phosphate transfer. May be the secondary sensor for CO. Donates a phosphate group to DevR (DosR). Publication Abstract from PubMed The sensor histidine kinases of Mycobacterium tuberculosis, DosS and DosT, are responsible for sensing hypoxic conditions and consist of sensor and kinase cores responsible for accepting signals and phosphorylation activity, respectively. The kinase core contains a dimerization and histidine phosphate-accepting (DHp) domain and an ATP binding domain (ABD). The 13 histidine kinase genes of M. tuberculosis can be grouped based on the presence or absence of the ATP-lid motif and F box (elements known to play roles in ATP binding) in their ABDs; DosS and DosT have ABDs lacking both these elements, and the crystal structures of their ABDs indicated they were unsuitable for ATP binding, as a short loop covers the putative ATP binding site. Although the ABD alone cannot bind ATP, the kinase core is functional in autophosphorylation. Appropriate spatial arrangement of the ABD and DHp domain within the kinase core is required for both autophosphorylation and ATP binding. An ionic interaction between R440 in the DHp domain and E537 in the short loop of the ABD is available and may open the ATP binding site, by repositioning the short loop away from the site. Mutations at R440 and E537 reduce autophosphorylation activity. Unlike other histidine kinases containing an ATP-lid, which protects bound ATP, DosS is unable to accept ATP until the ABD is properly positioned relative to the histidine; this may prevent unexpected ATP reactions. ATP binding can, therefore, function as a control mechanism for histidine kinase activity. Activation of ATP binding for the autophosphorylation of DosS, a Mycobacterium tuberculosis histidine kinase lacking an ATP-lid motif.,Cho HY, Lee YH, Bae YS, Kim E, Kang BS J Biol Chem. 2013 Mar 13. PMID:23486471 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 3zxq, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image