6fgk

Crystal structure of the small alarmone synthethase 2 from Bacillus subtilisCrystal structure of the small alarmone synthethase 2 from Bacillus subtilis

Structural highlights

6fgk is a 4 chain structure with sequence from Bacsu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	6fhj
Gene:	ywaC, BSU38480, ipa-7d (BACSU)
Activity:	GTP diphosphokinase, with EC number 2.7.6.5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[YWAC_BACSU] Functions as a (p)ppGpp synthase; GDP can be used instead of GTP, resulting in an increase of (p)ppGpp synthesis (PubMed:18067544). Overexpression in relA mutants (triple relA-yjbM-ywaC deletions and single relA deletions) leads to growth arrest; GTP levels fall drastically, various guanine-related nucleotides are synthesized (ppGp or pGpp), the cellular transcriptional profile changes dramatically and 70S ribosome dimerization occurs (PubMed:22950019). Overexpression in the presence of a wild-type relA gene does not have these effects (PubMed:22950019). 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. activities in response to changes in nutritional abundance. YwaC has probably a minor role in stringent response (PubMed:18067544).^[1] ^[2]

Publication Abstract from PubMed

The nutritional alarmones ppGpp and pppGpp (collectively: (p)ppGpp) are nucleotide-based second messengers enabling bacteria to respond to environmental and stress conditions. Several bacterial species contain two highly homologous (p)ppGpp synthetases named RelP (SAS2, YwaC) and RelQ (SAS1, YjbM). It is established that RelQ forms homotetramers that are subject to positive allosteric regulation by pppGpp, but structural and mechanistic insights into RelP lack behind. Here we present a structural and mechanistic characterization of RelP. In stark contrast to RelQ, RelP is not allosterically regulated by pppGpp and displays a different enzyme kinetic behavior. This discrepancy is evoked by different conformational properties of the guanosine-substrate binding site (G-Loop) of both proteins. Our study shows how minor structural divergences between close homologues result in new functional features during the course of molecular evolution.

Structural and mechanistic divergence of the small (p)ppGpp synthetases RelP and RelQ.,Steinchen W, Vogt MS, Altegoer F, Giammarinaro PI, Horvatek P, Wolz C, Bange G Sci Rep. 2018 Feb 1;8(1):2195. doi: 10.1038/s41598-018-20634-4. PMID:29391580^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nanamiya H, Kasai K, Nozawa A, Yun CS, Narisawa T, Murakami K, Natori Y, Kawamura F, Tozawa Y. Identification and functional analysis of novel (p)ppGpp synthetase genes in Bacillus subtilis. Mol Microbiol. 2008 Jan;67(2):291-304. Epub 2007 Dec 7. PMID:18067544 doi:http://dx.doi.org/10.1111/j.1365-2958.2007.06018.x
↑ Tagami K, Nanamiya H, Kazo Y, Maehashi M, Suzuki S, Namba E, Hoshiya M, Hanai R, Tozawa Y, Morimoto T, Ogasawara N, Kageyama Y, Ara K, Ozaki K, Yoshida M, Kuroiwa H, Kuroiwa T, Ohashi Y, Kawamura F. Expression of a small (p)ppGpp synthetase, YwaC, in the (p)ppGpp(0) mutant of Bacillus subtilis triggers YvyD-dependent dimerization of ribosome. Microbiologyopen. 2012 Jun;1(2):115-34. doi: 10.1002/mbo3.16. PMID:22950019 doi:http://dx.doi.org/10.1002/mbo3.16
↑ Steinchen W, Vogt MS, Altegoer F, Giammarinaro PI, Horvatek P, Wolz C, Bange G. Structural and mechanistic divergence of the small (p)ppGpp synthetases RelP and RelQ. Sci Rep. 2018 Feb 1;8(1):2195. doi: 10.1038/s41598-018-20634-4. PMID:29391580 doi:http://dx.doi.org/10.1038/s41598-018-20634-4

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OCA

[1] Nanamiya H, Kasai K, Nozawa A, Yun CS, Narisawa T, Murakami K, Natori Y, Kawamura F, Tozawa Y. Identification and functional analysis of novel (p)ppGpp synthetase genes in Bacillus subtilis. Mol Microbiol. 2008 Jan;67(2):291-304. Epub 2007 Dec 7. PMID:18067544 doi:http://dx.doi.org/10.1111/j.1365-2958.2007.06018.x

[2] Tagami K, Nanamiya H, Kazo Y, Maehashi M, Suzuki S, Namba E, Hoshiya M, Hanai R, Tozawa Y, Morimoto T, Ogasawara N, Kageyama Y, Ara K, Ozaki K, Yoshida M, Kuroiwa H, Kuroiwa T, Ohashi Y, Kawamura F. Expression of a small (p)ppGpp synthetase, YwaC, in the (p)ppGpp(0) mutant of Bacillus subtilis triggers YvyD-dependent dimerization of ribosome. Microbiologyopen. 2012 Jun;1(2):115-34. doi: 10.1002/mbo3.16. PMID:22950019 doi:http://dx.doi.org/10.1002/mbo3.16

[3] Steinchen W, Vogt MS, Altegoer F, Giammarinaro PI, Horvatek P, Wolz C, Bange G. Structural and mechanistic divergence of the small (p)ppGpp synthetases RelP and RelQ. Sci Rep. 2018 Feb 1;8(1):2195. doi: 10.1038/s41598-018-20634-4. PMID:29391580 doi:http://dx.doi.org/10.1038/s41598-018-20634-4

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