glmM

glmM
168

phosphoglucosamine mutase, required for cell wall synthesis, inhibits CdaA activity

Locus
BSU_01770
Molecular weight
48.27 kDa
Isoelectric point
4.68
Protein length
448 aaSequenceBlast
Gene length
1347 bpSequenceBlast
Function
cell wall synthesis, control of c-di-AMP synthesis
Product
phosphoglucosamine mutase, required for cell wall synthesis
Essential
yes
E.C.
5.4.2.10
Synonyms
glmM, ybbT
Outlinks
BsubCyc SubtiList UniProt STRING Genoscapist PaperBLAST

Genomic Context

List of homologs in different organisms, belongs to COG1109 (Galperin et al., 2021)

This gene is a member of the following regulons

SigA regulon, GlmS ribozyme

Gene
Coordinates
198,497 → 199,843
Phenotypes of a mutant
essential PubMed
The protein
Catalyzed reaction/ biological activity
D-glucosamine 6-phosphate --> α-D-glucosamine 1-phosphate (according to UniProt)
inhibition of CdaA activity (PubMed) under conditions of osmotic stress (demonstrated in L. monocytogenes ) PubMed
Protein family
phosphohexose mutase family (with PgcA, PubMed)
Structure
7OML (PDB)
7OLH (PDB), 7OJS (PDB) (complex of the CdaA DAC domain and GlmM)
3PDK (PDB) (from B. anthracis) PubMed
O34824 (AlphaFold)
Modification
phosphorylation on Ser-100 PubMed, this is an autophosphorylation  PubMed
Expression and Regulation
Operons
Genes
cdaA-cdaR-glmM-glmS
Description
PubMed
Regulatory mechanism
GlmS ribozyme: RNA switch, in GlmS ribozyme
Sigma factors
SigA: sigma factor, PubMed, in sigA regulon
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cdaA→glmS

2025-03-28 05:21:56

Jstuelk

149

d0e388855d436414f58a0fe3c7427dc65a267c07

DAD2D234926A5513FEB7883AAB4D651657324B25

Biological materials
Expression vectors
pGP400: (expression in B. subtilis in pBQ200), available in Jörg Stülke's lab
pGP1401: (expression, purification in E. coli with N-terminal His-tag, in pWH844), available in Jörg Stülke's lab
pGP1402: (cloning vector for glmM (GlmM S100A) in E. coli, in pBlueskript KS), available in Jörg Stülke's lab
pGP1403: (expression of GlmM (S100A) in B. subtilis in pBQ200), available in Jörg Stülke's lab
pGP1405: (expression, purification of GlmM (S100A) in E. coli with N-terminal His-tag, in pWH844), available in Jörg Stülke's lab
Two-hybrid system
B. pertussis adenylate cyclase-based bacterial two hybrid system (BACTH), available in Jörg Stülke's lab
FLAG-tag construct
GP1380 lacA::cdaR-Strep aphA3 glmM-3xFLAG ermC (based on pGP1460 and pGP1087), available in Jörg Stülke's lab
LacZ fusion
GP1340 (cat) based on pAC6, available in Jörg Stülke's lab PubMed
Antibody
available in Jörg Stülke's lab
GFP fusion
GP1382 glmM-gfp ermC (based on pGP1080), available in Jörg Stülke's lab
References
Reviews
Herzberg C, Meißner J, Warneke R, Stülke JThe many roles of cyclic di-AMP to control the physiology of Bacillus subtilis.microLife. 2023; 4:uqad043. PMID: 37954098
Stiers KM, Muenks AG, Beamer LJ Biology, Mechanism, and Structure of Enzymes in the α-d-Phosphohexomutase Superfamily. Advances in protein chemistry and structural biology. 2017; 109:265-304. pii:S1876-1623(17)30036-6. doi:10.1016/bs.apcsb.2017.04.005. PMID:28683921
Barreteau H, Kovac A, Boniface A, Sova M, Gobec S, Blanot D Cytoplasmic steps of peptidoglycan biosynthesis. FEMS microbiology reviews. 2008 Mar; 32(2):168-207. doi:10.1111/j.1574-6976.2008.00104.x. PMID:18266853
Original Publications
Pathania M, Tosi T, Millership C, Hoshiga F, Morgan RML, Freemont PS, Gründling AStructural basis for the inhibition of the Bacillus subtilis c-di-AMP cyclase CdaA by the phosphoglucomutase GlmM.The Journal of biological chemistry. 2021 Oct 19; :101317. PMID: 34678313
Gibhardt J, Heidemann JL, Bremenkamp R, Rosenberg J, Seifert R, Kaever V, Ficner R, Commichau FM An extracytoplasmic protein and a moonlighting enzyme modulate synthesis of c-di-AMP in Listeria monocytogenes. Environmental microbiology. 2020 Apr 06; . doi:10.1111/1462-2920.15008. PMID:32250026
Patel V, Black KA, Rhee KY, Helmann JD Bacillus subtilis PgcA moonlights as a phosphoglucosamine mutase in support of peptidoglycan synthesis. PLoS genetics. 2019 Oct 07; 15(10):e1008434. doi:10.1371/journal.pgen.1008434. PMID:31589605
Tosi T, Hoshiga F, Millership C, Singh R, Eldrid C, Patin D, Mengin-Lecreulx D, Thalassinos K, Freemont P, Gründling A Inhibition of the Staphylococcus aureus c-di-AMP cyclase DacA by direct interaction with the phosphoglucosamine mutase GlmM. PLoS pathogens. 2019 Jan 22; 15(1):e1007537. doi:10.1371/journal.ppat.1007537. PMID:30668586
Zhu Y, Pham TH, Nhiep TH, Vu NM, Marcellin E, Chakrabortti A, Wang Y, Waanders J, Lo R, Huston WM, Bansal N, Nielsen LK, Liang ZX, Turner MS Cyclic-di-AMP synthesis by the diadenylate cyclase CdaA is modulated by the peptidoglycan biosynthesis enzyme GlmM in Lactococcus lactis. Molecular microbiology. 2016 Mar; 99(6):1015-27. doi:10.1111/mmi.13281. PMID:26585449
Gundlach J, Mehne FM, Herzberg C, Kampf J, Valerius O, Kaever V, Stülke J An Essential Poison: Synthesis and Degradation of Cyclic Di-AMP in Bacillus subtilis. Journal of bacteriology. 2015 Oct; 197(20):3265-74. doi:10.1128/JB.00564-15. PMID:26240071
Mehne FM, Gunka K, Eilers H, Herzberg C, Kaever V, Stülke J Cyclic di-AMP homeostasis in bacillus subtilis: both lack and high level accumulation of the nucleotide are detrimental for cell growth. The Journal of biological chemistry. 2013 Jan 18; 288(3):2004-17. doi:10.1074/jbc.M112.395491. PMID:23192352
Luo Y, Helmann JD Analysis of the role of Bacillus subtilis σ(M) in β-lactam resistance reveals an essential role for c-di-AMP in peptidoglycan homeostasis. Molecular microbiology. 2012 Feb; 83(3):623-39. doi:10.1111/j.1365-2958.2011.07953.x. PMID:22211522
Mehra-Chaudhary R, Mick J, Beamer LJ Crystal structure of Bacillus anthracis phosphoglucosamine mutase, an enzyme in the peptidoglycan biosynthetic pathway. Journal of bacteriology. 2011 Aug; 193(16):4081-7. doi:10.1128/JB.00418-11. PMID:21685296
Irnov I, Sharma CM, Vogel J, Winkler WC Identification of regulatory RNAs in Bacillus subtilis. Nucleic acids research. 2010 Oct; 38(19):6637-51. doi:10.1093/nar/gkq454. PMID:20525796
Schmidl SR, Gronau K, Pietack N, Hecker M, Becher D, Stülke J The phosphoproteome of the minimal bacterium Mycoplasma pneumoniae: analysis of the complete known Ser/Thr kinome suggests the existence of novel kinases. Molecular & cellular proteomics : MCP. 2010 Jun; 9(6):1228-42. doi:10.1074/mcp.M900267-MCP200. PMID:20097688
Eymann C, Becher D, Bernhardt J, Gronau K, Klutzny A, Hecker M Dynamics of protein phosphorylation on Ser/Thr/Tyr in Bacillus subtilis. Proteomics. 2007 Oct; 7(19):3509-26. . PMID:17726680
Macek B, Mijakovic I, Olsen JV, Gnad F, Kumar C, Jensen PR, Mann M The serine/threonine/tyrosine phosphoproteome of the model bacterium Bacillus subtilis. Molecular & cellular proteomics : MCP. 2007 Apr; 6(4):697-707. . PMID:17218307
Shackelford GS, Regni CA, Beamer LJ Evolutionary trace analysis of the alpha-D-phosphohexomutase superfamily. Protein science : a publication of the Protein Society. 2004 Aug; 13(8):2130-8. . PMID:15238632
Jolly L, Pompeo F, van Heijenoort J, Fassy F, Mengin-Lecreulx D Autophosphorylation of phosphoglucosamine mutase from Escherichia coli. Journal of bacteriology. 2000 Mar; 182(5):1280-5. . PMID:10671448
Jolly L, Ferrari P, Blanot D, Van Heijenoort J, Fassy F, Mengin-Lecreulx D Reaction mechanism of phosphoglucosamine mutase from Escherichia coli. European journal of biochemistry. 1999 May; 262(1):202-10. . PMID:10231382
Mengin-Lecreulx D, van Heijenoort J Characterization of the essential gene glmM encoding phosphoglucosamine mutase in Escherichia coli. The Journal of biological chemistry. 1996 Jan 05; 271(1):32-9. . PMID:8550580

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Time of last update: 2025-04-07 04:12:51

Author of last update: Jstuelk