5dec

Crystal structure of the small alarmone synthetase 1 from Bacillus subtilis

spinqualitylabelsall models 5dec, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5dec is a 4 chain structure with sequence from Bacillus subtilis subsp. subtilis str. 168. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function YJBM_BACSU Functions as a (p)ppGpp synthase. In eubacteria ppGpp (guanosine 3'-diphosphate 5-' diphosphate) is a mediator of the stringent response that coordinates a variety of cellular activities in response to changes in nutritional abundance. YjbM has probably a minor role in stringent response. Publication Abstract from PubMed Nucleotide-based second messengers serve in the response of living organisms to environmental changes. In bacteria and plant chloroplasts, guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) [collectively named "(p)ppGpp"] act as alarmones that globally reprogram cellular physiology during various stress conditions. Enzymes of the RelA/SpoT homology (RSH) family synthesize (p)ppGpp by transferring pyrophosphate from ATP to GDP or GTP. Little is known about the catalytic mechanism and regulation of alarmone synthesis. It also is unclear whether ppGpp and pppGpp execute different functions. Here, we unravel the mechanism and allosteric regulation of the highly cooperative alarmone synthetase small alarmone synthetase 1 (SAS1) from Bacillus subtilis. We determine that the catalytic pathway of (p)ppGpp synthesis involves a sequentially ordered substrate binding, activation of ATP in a strained conformation, and transfer of pyrophosphate through a nucleophilic substitution (SN2) reaction. We show that pppGpp-but not ppGpp-positively regulates SAS1 at an allosteric site. Although the physiological significance remains to be elucidated, we establish the structural and mechanistic basis for a biological activity in which ppGpp and pppGpp execute different functional roles. Catalytic mechanism and allosteric regulation of an oligomeric (p)ppGpp synthetase by an alarmone.,Steinchen W, Schuhmacher JS, Altegoer F, Fage CD, Srinivasan V, Linne U, Marahiel MA, Bange G Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13348-53. doi:, 10.1073/pnas.1505271112. Epub 2015 Oct 12. PMID:26460002 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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