The methyltransferase NmbA methylates the low-molecular weight thiol bacillithiol, and displays a specific structural architecture
Open accessPublished version of a preprint
Abstract
Low-molecular-weight (LMW) thiols maintain the cellular redox balance and protect cells against reactive species, heavy metals, toxins, and antibiotics. Despite having similar metabolic functions, structurally distinct LMW thiols are widespread in nature, with bacillithiol (BSH) being the predominant LMW thiol in bacteria. The LMW thiol N-methyl-BSH (N-Me-BSH) has been identified in the green sulfur bacterium Chlorobaculum tepidum, revealing the presence of a putative S-adenosyl-l-methionine (SAM)-dependent methyltransferase (MT), NmbA, which could catalyze the final biosynthetic step of N-Me-BSH. In this study, we report biochemical evidence for NmbA's specific function as an MT of the N-atom of the BSH cysteine moiety. We also present the crystal structure of NmbA, confirming that NmbA is a Class I SAM-dependent MT, however, displaying a unique three-dimensional architecture that differs from those of other natural product MTs (NPMTs). The NmbA active site has a narrow molecular basket structure resulting from an unusual organization of the variable Cap domain, and our docking calculations suggests that it can specifically accommodate the BSH substrate. Our research provides a valuable overview of the phylogenetic distribution of N-Me-BSH in bacteria, alongside essential functional and structural insight into a new class of N-directed NPMTs. These findings contribute to the field of SAM-dependent MTs and may allow for targeting distinct bacterial defense mechanisms involving LMW thiols with potential environmental, biotechnological, and medical implications.
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Cites
Cytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888 · cited 1× · see citing works
“Figures illustrating SSN analyses were created in Cytoscape (version 3.9) with the organic layout [54].”
InfluentialMAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability
Katoh, K., & Standley, D. M. (2013) · Molecular Biology and Evolution · doi:10.1093/molbev/mst010 · Cited by 46,209 · cited 1× · see citing works
“The analysis was based on identification of homologous sequences from the UniRef90 database using the HMMER algorithm [51], and multiple sequence alignment with MAFFT [52].”
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. D. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 27,510 · cited 1× · see citing works
“The first rounds of refinements were performed using restrained refinement in REFMAC5 [63] followed by several cycles of refinement with phenix. refine [64] in the Phenix suite [65] performed in iterative cycles with model building performed in Coot [66].”
<i>PHENIX</i> : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716 · cited 1× · see citing works
“The first rounds of refinements were performed using restrained refinement in REFMAC5 [63] followed by several cycles of refinement with phenix. refine [64] in the Phenix suite [65] performed in iterative cycles with model building performed in Coot [66].”
<i>Phaser</i> crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612 · cited 1× · see citing works
“The Ct NmbA structure was solved with molecular replacement (MR) with PHASER [59] using a search model of Ct NmbA from the AlphaFold Protein Structure Database [60,61] (Uniprot: Q8KDK7) with a TFZ score of 8.3 and 17.8 for the two molecules in the asymmetric unit.”
InfluentialFast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega
Sievers, F., Wilm, A., Dineen, D., Gibson, T., Karplus, K., Li, W.-Z., Lopez, R., McWilliam, H., Remmert, M., Söding, J., et al. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.75 · Cited by 15,576 · cited 1× · see citing works
“The CT1040 homologous sequences passing the criteria were multiple sequence aligned in JalView [46] with Clustal Omega [47] and phylogenetic tree analysis was done using average distances using the BLOSUM62 matrix.”
<i>MolProbity</i> : all-atom structure validation for macromolecular crystallography
Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115 · cited 1× · see citing works
“Model validation was performed using MolProbity [67].”
Overview of the <i>CCP</i> 4 suite and current developments
Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., Keegan, R. M., Krissinel, E. B., Leslie, A. G. W., McCoy, A., et al. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910045749 · Cited by 12,353 · cited 1× · see citing works
“The diffraction data of Ct NmbA crystals were indexed and integrated through auto-processing with autoPROC [56] and XDS [57], and scaled and merged with Aimless in the CCP4 package [58].”
Inference of macromolecular assemblies from crystalline state.
Krissinel, E., & Henrick, K. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.05.022 · Cited by 10,189 · cited 1× · see citing works
“PDBePISA [69] was used to confirm that NmbA is a biological monomer, despite having two monomers in the asymmetric unit, since analysis of the protein interfaces did not reveal any specific interactions that could result in the formation of a stable quaternary structure.”
Seshadri, R. (2004) · doi:10.29172/6af5be88489f4a509abf998e8912254a · Cited by 7,056
Towards automated crystallographic structure refinement with <i>phenix.refine</i>
Afonine, P. V., Grosse-Kunstleve, R. W., Echols, N., Headd, J. J., Moriarty, N. W., Mustyakimov, M., Terwilliger, T. C., Urzhumtsev, A., Zwart, P. H., & Adams, P. D. (2012) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444912001308 · Cited by 5,511 · cited 1× · see citing works
“The first rounds of refinements were performed using restrained refinement in REFMAC5 [63] followed by several cycles of refinement with phenix. refine [64] in the Phenix suite [65] performed in iterative cycles with model building performed in Coot [66].”
Calculation of protein extinction coefficients from amino acid sequence data.
Gill, S., & von Hippel, P. H. (1989) · Analytical Biochemistry · doi:10.1016/0003-2697(89)90602-7 · Cited by 5,382 · see citing works
Ashkenazy, H., Abadi, S., Martz, E., Chay, O., Mayrose, I., Pupko, T., & Ben-Tal, N. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw408 · Cited by 3,163 · cited 1× · see citing works
“The degree of conservation of residues in the Ct NmbA structure was evaluated with ConSurf [48 – 50].”
Liu, Y., Yang, X., Gan, J., Chen, S., Xiao, Z. J., & Cao, Y. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac394 · Cited by 2,216 · cited 1× · see citing works
“Structure-based blind-docking calculations between Ct NmbA and BSH were performed with CB-Dock 2 ( Cavity-detection guided Blind Docking ) [72].”
Varadi, M., Bertoni, D., Magana, P., Paramval, U., Pidruchna, I., Radhakrishnan, M., Tsenkov, M., Nair, S., Mirdita, M., Yeo, J., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkad1011 · Cited by 2,052 · cited 1× · see citing works
“The Ct NmbA structure was solved with molecular replacement (MR) with PHASER [59] using a search model of Ct NmbA from the AlphaFold Protein Structure Database [60,61] (Uniprot: Q8KDK7) with a TFZ score of 8.3 and 17.8 for the two molecules in the asymmetric unit.”
InfluentialAshkenazy, H., Erez, E., Martz, E., Pupko, T., & Ben‐Tal, N. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq399 · Cited by 1,822 · cited 1× · see citing works
“The degree of conservation of residues in the Ct NmbA structure was evaluated with ConSurf [48 – 50].”
PDBsum: Structural summaries of PDB entries
Laskowski, R., Jabłońska, J., Pravda, L., Vareková, R., & Thornton, J. (2017) · Protein Science · doi:10.1002/pro.3289 · Cited by 1,650 · cited 1× · see citing works
“The secondary structure toplogy diagram for Ct NmbA was generated with PDBsum [70] and manually adjusted and colored.”
Dali server: structural unification of protein families
Holm, L. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac387 · Cited by 913 · cited 1× · see citing works
“A search for similar structures to NmbA in the Protein Data Bank (PDB) was performed with the DALI (Distance-matrix ALIgnment) protein structure-comparison server [71] using the Ct NmbA structure as a search template.”
Finn, R. D., Clements, J., Arndt, W. D., Miller, B. L., Wheeler, T. J., Schreiber, F., Bateman, A. G., & Eddy, S. R. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv397 · Cited by 911 · cited 1× · see citing works
“The analysis was based on identification of homologous sequences from the UniRef90 database using the HMMER algorithm [51], and multiple sequence alignment with MAFFT [52].”
Many paths to methyltransfer: a chronicle of convergence
Schubert, H. L., Blumenthal, R. M., & Cheng, X. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00090-2 · Cited by 876 · cited 1× · see citing works
“The fold is made up by alternating α -helices and β -strands, with a core seven β -strand (7BS) sheet sandwiched by the α -helices, serving as a SAM-binding domain [37,40].”
Valid publication of the names of forty-two phyla of prokaryotes.
Oren, A., & Garrity, G. (2021) · International Journal of Systematic and Evolutionary Microbiology · doi:10.1099/ijsem.0.005056 · Cited by 790 · cited 2× · see citing works
“For the microbials, all phyla that have been validly published according to the Bacteriological Code [34,35] were searched.”
D2P2: database of disordered protein predictions
Oates, M. E., Romero, P., Ishida, T., Ghalwash, M., Mizianty, M. J., Xue, B., Dosztányi, Z., Uversky, V. N., Obradovic, Z., Kurgan, L., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1226 · Cited by 705 · cited 1× · see citing works
“The disorder of these residues was also indicated by the D 2 P 2 : Database of Disorder Protein Predictions [62].”
SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold.
Martin, J. L., & Mcmillan, F. M. (2002) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(02)00391-3 · Cited by 581 · cited 3× · see citing works
“The fold is made up by alternating α -helices and β -strands, with a core seven β -strand (7BS) sheet sandwiched by the α -helices, serving as a SAM-binding domain [37,40].”
ConSurf: Using Evolutionary Data to Raise Testable Hypotheses about Protein Function
Celniker, G., Nimrod, G., Ashkenazy, H., Glaser, F., Martz, E., Mayrose, I., Pupko, T., & Ben‐Tal, N. (2013) · Israel Journal of Chemistry · doi:10.1002/ijch.201200096 · Cited by 551 · see citing works
Distribution of thiols in microorganisms: mycothiol is a major thiol in most actinomycetes
Newton, G. L., Arnold, K., Price, M. S., Sherrill, C., Delcardayre, S. B., Aharonowitz, Y., Cohen, G., Davies, J., Fahey, R. C., & Davis, C. (1996) · Journal of Bacteriology · doi:10.1128/jb.178.7.1990-1995.1996 · Cited by 523 · see citing works
Occurrence of glutathione in bacteria
Fahey, R. C., Brown, W., Adams, W. B., & Worsham, M. B. (1978) · Journal of Bacteriology · doi:10.1128/jb.133.3.1126-1129.1978 · Cited by 522 · cited 1× · see citing works
“Eukaryotes and most Gram-negative bacteria use the extensively studied glutathione (GSH) as their main LMW thiol [5,6].”
The Many Faces of Glutathione in Bacteria
Masip, L., Veeravalli, K., & Georgiou, G. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.753 · Cited by 478 · cited 1× · see citing works
“Eukaryotes and most Gram-negative bacteria use the extensively studied glutathione (GSH) as their main LMW thiol [5,6].”
Crystal structure of catechol O-methyltransferase
Vidgren, J., Svensson, L., & Liljas, A. (1994) · Nature · doi:10.1038/368354a0 · Cited by 403 · cited 1× · see citing works
“The majority belong to the large Class I MTs, dominated by a Rossmann-like fold, which was also seen for the first reported crystal structure of an NPMT, catechol O-MT (COMT) [39].”
Oberg, N., Zallot, R., & Gerlt, J. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168018 · Cited by 358 · see citing works
Methylated arsenic species in plants originate from soil microorganisms.
Lomax, C., Liu, W.-J., Wu, L.-Y., Xue, K., Xiong, J., Zhou, J., McGrath, S., Meharg, A., Miller, A., & Zhao, F.-J. (2012) · New Phytologist · doi:10.1111/j.1469-8137.2011.03956.x · Cited by 343 · see citing works
Natural history of S-adenosylmethionine-binding proteins
Kozbial, P., & Mushegian, A. (2005) · BMC Structural Biology · doi:10.1186/1472-6807-5-19 · Cited by 287 · cited 2× · see citing works
“Herein, NmbA contains a VLDIAxGxG motif, corresponding to the conserved amino acid block with the consensus sequence (V/I/L)(L/V)(D/E)(V/I)-GxGxG found in MTs [38,41].”
Architectures, mechanisms and molecular evolution of natural product methyltransferases.
Liscombe, D., Louie, G., & Noel, J. (2012) · Natural product reports (Print) · doi:10.1039/c2np20029e · Cited by 285 · cited 1× · see citing works
“In the biosynthesis of natural products, methylation of primary and secondary metabolites is a common chemical modification, catalyzed by small molecule, or natural product, SAM-dependent MTs (NPMTs) [27].”
Bacillithiol is an antioxidant thiol produced in Bacilli
Newton, G., Rawat, M., Clair, J. L. L., Jothivasan, V. K., Budiarto, T. M., Hamilton, C., Claiborne, A., Helmann, J., & Fahey, R. C. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.189 · Cited by 283 · cited 1× · see citing works
“Firmicutes (Bacillota) (low-G + C Gram-positive bacteria), including Staphylococcus aureus and many bacilli, utilize bacillithiol (BSH, Cys-GlcN-Mal) [14 – 16].”
Fahey, R. C. (2001) · Annual Review of Microbiology · doi:10.1146/annurev.micro.55.1.333 · Cited by 266 · cited 1× · see citing works
“Studies have demonstrated that most bacteria (and some eukaryotes) do not produce GSH, and rely on alternative and unique thiol-redox buffers [7,8].”
Biosynthesis and functions of bacillithiol, a major low-molecular-weight thiol in Bacilli
Gaballa, A., Newton, G., Antelmann, H., Parsonage, D., Upton, H. E., Rawat, M., Claiborne, A., Fahey, R. C., & Helmann, J. (2010) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1000928107 · Cited by 249 · cited 1× · see citing works
“In addition to the BSH biosynthesis genes bshA, bshB, and bshC [15, 25,26], C. tepidum was found to contain two orthologs of putative S -adenosyl- L -methionine (SAM)-dependent methyltransferases (MTs), CT1213 and CT1040 , where the latter was identified as the in vivo BSH MT, designated NmbA ( N…”
A complex thiolate switch regulates the Bacillus subtilis organic peroxide sensor OhrR
Lee, J., Soonsanga, S., & Helmann, J. D. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702081104 · Cited by 244 · see citing works
Romero, F., Espliego, F., Baz, J. P., de Quesada, T. G., Gravalos, D., de la Calle, F., & Fernández-Puentes, J. L. (1997) · Journal of antibiotics (Tokyo. 1968) · doi:10.7164/antibiotics.50.734 · Cited by 212 · cited 1× · see citing works
“N -methylation of cysteine, however, is rare, and N -Me-BSH is regarded as the first reported case of cysteine N -methylation catalyzed by a putative standalone methyl transferase [31 – 33], which highlights the importance to further characterize NmbA.”
Glutathione analogs in prokaryotes.
Fahey, R. C. (2013) · Biochimica et Biophysica Acta · doi:10.1016/j.bbagen.2012.10.006 · Cited by 205 · cited 1× · see citing works
“These include the structurally distinct LMW thiols trypanothione, γ -gluta- mylcysteine, ergothioneine, ovothiol, and glutathione amide [1,9].”
Methyltransferases: Functions and Applications
Abdelraheem, E. M. M., Thair, B., Varela, R. F., Jockmann, E., Popadić, D., Hailes, H. C., Ward, J. M., Iribarren, A. M., Lewkowicz, E. S., Andexer, J. N., et al. (2022) · ChemBioChem · doi:10.1002/cbic.202200212 · Cited by 200 · see citing works
RADDOSE-3D: time- and space-resolved modelling of dose in macromolecular crystallography
Zeldin, O., Gerstel, M., & Garman, E. (2013) · Journal of Applied Crystallography · doi:10.1107/s0021889813011461 · Cited by 193 · cited 1× · see citing works
“The absorbed X-ray dose was calculated using the program RADDOSE-3D [68].”
Pothecary, R. (2021) · Running Microsoft Workloads on AWS · doi:10.1007/978-1-4842-6628-1_3 · Cited by 184 · cited 1×
“A search for similar structures to NmbA in the Protein Data Bank (PDB) was performed with the DALI (Distance-matrix ALIgnment) protein structure-comparison server 67 using the Ct NmbA structure as a search template.”
Redox regulation by reversible protein S-thiolation in bacteria
Vu, L. V., Rossius, M., & Antelmann, H. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00187 · Cited by 173 · cited 1× · see citing works
“These antioxidants help to preserve a reducing intracellular environment, function as thiol co-factors in scavenging reactive species, detoxifying toxins and antibiotics, protecting cells against heavy metals, and regulating and protecting exposed protein thiols through S -thiolation [1 – 4].”
Low-Molecular-Weight Thiols in Thiol–Disulfide Exchange
Laer, K. V., Hamilton, C. J., & Messens, J. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4964 · Cited by 159 · see citing works
Spies, H. S., & Steenkamp, D. (1994) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1994.tb20013.x · Cited by 153 · cited 1× · see citing works
“Firmicutes (Bacillota) (low-G + C Gram-positive bacteria), including Staphylococcus aureus and many bacilli, utilize bacillithiol (BSH, Cys-GlcN-Mal) [14 – 16].”
The Role of Bacillithiol in Gram-Positive <i>Firmicutes</i>
Chandrangsu, P., Loi, V. V., Antelmann, H., & Helmann, J. D. (2018) · Antioxidants & Redox Signaling · doi:10.1089/ars.2017.7057 · Cited by 120 · see citing works
Patel, H. M., & Walsh, C. T. (2001) · Biochemistry · doi:10.1021/bi010519n · Cited by 112 · cited 1× · see citing works
“N -methylation of cysteine, however, is rare, and N -Me-BSH is regarded as the first reported case of cysteine N -methylation catalyzed by a putative standalone methyl transferase [31 – 33], which highlights the importance to further characterize NmbA.”
LaFrentz, B., Králová, S., Burbick, C., Alexander, T. L., Phillips, C., Griffin, M., Waldbieser, G., García, J., Sebastião, F. D. A., Soto, E., et al. (2021) · Systematic and Applied Microbiology · doi:10.1016/j.syapm.2021.126293 · Cited by 107 · cited 1× · see citing works
“Examples include Flavobacterium columnare , the causative agent of columnaris disease in freshwater fish [36], posing a serious threat to fish farming and fish populations worldwide.”
Khanh, B., Roberts, A. A., Huyền, T. T. T., Bäsell, K., Becher, D., Albrecht, D., Hamilton, C. J., & Antelmann, H. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4686 · Cited by 87 · cited 1× · see citing works
“In the latter case, this ultimately leads to the formation of the bacillithiol disulfide (BSSB) [17 – 19].”
In silico analysis of methyltransferase domains involved in biosynthesis of secondary metabolites
Ansari, M. Z., Sharma, J., Gokhale, R., & Mohanty, D. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-454 · Cited by 86 · cited 1×
“Unraveling the exact mechanism employed by NmbA requires further studies.”
Sakuda, S., Zhou, Z., & Yamada, Y. (1994) · Bioscience, biotechnology and biochemistry · doi:10.1271/bbb.58.1347 · Cited by 65 · see citing works
Chemistry and Redox Biology of Mycothiol
Reyes, A. M., Pedre, B., De Armas, M. I., Tossounian, M.-A., Radi, R., Messens, J., & Trujillo, M. (2018) · Antioxidants & Redox Signaling · doi:10.1089/ars.2017.7074 · Cited by 64 · cited 1× · see citing works
“In Actinobacteria (high-G + C Gram-positive bacteria), such as mycobacteria, Streptomycetes and corynebacteria, mycothiol (MSH) serves as the predominant LMW thiol [10 – 13].”
Gaballa, A., Bùi, C. L. K., Roberts, A., Becher, D., Hamilton, C., Antelmann, H., & Helmann, J. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5327 · Cited by 62 · cited 1× · see citing works
“Alternatively, BSH can react directly with ROS, again leading to the oxidation of BSH to BSSB [20].”
Sharma, S. V., Jothivasan, V. K., Newton, G., Upton, H. E., Wakabayashi, J. I., Kane, M., Roberts, A., Rawat, M., Clair, J. L. L., & Hamilton, C. (2011) · Angewandte Chemie · doi:10.1002/anie.201100196 · Cited by 58 · cited 2×
“Firmicutes (Bacillota) (low-G + C Gram-positive bacteria), including Staphylococcus aureus and many bacilli, utilize bacillithiol (BSH, Cys-GlcN-Mal) [14 – 16].”
Aoki, S., Cao, L.-W., Matsui, K., Rachmat, R., Akiyama, S., & Kobayashi, M. (2004) · Tetrahedron · doi:10.1016/j.tet.2003.07.020 · Cited by 56 · see citing works
Schmidberger, J., James, A., Edwards, R., Naismith, J., & O'Hagan, D. (2010) · Angewandte Chemie · doi:10.1002/anie.201000119 · Cited by 51 · cited 1×
“MTs are classified based on the methyl-accepting atom, with the most abundant ones being O -directed MTs, but NPMTs also commonly methylate N , C , or less frequently S , in addition to other less typical types of acceptors [28 – 30].”
Linzner, N., Vu, L. V., Fritsch, V. N., Quach, T. N., Stenzel, S., Wirtz, M., Hell, R., Hamilton, C., Tedin, K., Fulde, M., et al. (2019) · bioRxiv · doi:10.3389/fmicb.2019.01355 · Cited by 42 · see citing works
Imber, M., Vu, L. V., Reznikov, S., Fritsch, V. N., Pietrzyk-Brzezińska, A. J., Prehn, J., Hamilton, C., Wahl, M., Bronowska, A., & Antelmann, H. (2018) · Redox Biology · doi:10.1016/j.redox.2018.02.001 · Cited by 42 · cited 1×
“In the latter case, this ultimately leads to the formation of the bacillithiol disulfide (BSSB) [17 – 19].”
Glutathione amide and its perthiol in anaerobic sulfur bacteria
Bartsch, R. G., Newton, G. L., Sherrill, C., & Fahey, R. C. (1996) · Journal of Bacteriology · doi:10.1128/jb.178.15.4742-4746.1996 · Cited by 40 · cited 1× · see citing works
“Furthermore, Gram-positive bacteria mainly produce two structurally distinct LMW thiols, involved in similar metabolic processes.”
Oren, A., Mareš, J., & Rippka, R. (2022) · International Journal of Systematic and Evolutionary Microbiology · doi:10.1099/ijsem.0.005528 · Cited by 37 · cited 2×
“For the microbials, all phyla that have been validly published according to the Bacteriological Code [34,35] were searched.”
Mikheyeva, I. V., Thomas, J. M., Kolar, S. L., Corvaglia, A., Gaïa, N., Léo, S., François, P., Liu, G. Y., Rawat, M., & Cheung, A. L. (2019) · Molecular Microbiology · doi:10.1111/mmi.14207 · Cited by 34 · cited 1× · see citing works
“The de-thiolation is catalyzed by glutaredoxins or bacilliredoxins in cells relying on GSH and BSH, respectively.”
Coiner, H. A., Schröder, G., Wehinger, E., Liu, C., Noel, J. P., Schwab, W. G., & Schröder, J. (2006) · The Plant Journal · doi:10.1111/j.1365-313x.2006.02680.x · Cited by 34 · cited 1× · see citing works
“MTs are classified based on the methyl-accepting atom, with the most abundant ones being O -directed MTs, but NPMTs also commonly methylate N , C , or less frequently S , in addition to other less typical types of acceptors [28 – 30].”
Fang, Z., Roberts, A., Weidman, K., Sharma, S. V., Claiborne, A., Hamilton, C., & Santos, P. D. D. (2013) · Biochemical Journal · doi:10.1042/bj20130415 · Cited by 25 · cited 1×
“In 2018, Hiras et al. reported the existence of another novel thiol from the anaerobic green sulfur bacterium Chlorobium tepidum , N -methyl-bacillithiol ( N -Me-BSH), which is a BSH derivative modified by N -methylation of the amino group in the cysteine moiety of BSH [24] (Scheme 1).”
Drinkwater, N., Gee, C., Puri, M., Criscione, K. R., McLeish, M., Grunewald, G. L., & Martin, J. L. (2009) · Biochemical Journal · doi:10.1042/bj20090702 · Cited by 25
Royer, C., & Cook, P. D. (2019) · Protein Science · doi:10.1002/pro.3617 · Cited by 18 · cited 1×
“In addition to the BSH biosynthesis genes bshA, bshB, and bshC [15, 25,26], C. tepidum was found to contain two orthologs of putative S -adenosyl- L -methionine (SAM)-dependent methyltransferases (MTs), CT1213 and CT1040 , where the latter was identified as the in vivo BSH MT, designated NmbA ( N…”
Hiras, J., Sharma, S. V., Raman, V., Tinson, R. A. J., Arbach, M., Rodrigues, D., Norambuena, J., Hamilton, C., & Hanson, T. E. (2018) · mBio · doi:10.1128/mbio.01603-18 · Cited by 16 · cited 5× · see citing works
“…genes bshA, bshB, and bshC [15, 25,26], C. tepidum was found to contain two orthologs of putative S -adenosyl- L -methionine (SAM)-dependent methyltransferases (MTs), CT1213 and CT1040 , where the latter was identified as the in vivo BSH MT, designated NmbA ( N -Me-BSH synthase A) [24].”
InfluentialHammerstad, M., Gudim, I., & Hersleth, H. (2020) · Biochemistry · doi:10.1021/acs.biochem.0c00745 · Cited by 14 · cited 1× · see citing works
“The de-thiolation is catalyzed by glutaredoxins or bacilliredoxins in cells relying on GSH and BSH, respectively.”
Self-citationStructure and possible mechanism of the CcbJ methyltransferase from Streptomyces caelestis.
Bauer, J., Ondrovičová, G., Najmanova, L., Pevala, V., Kameník, Z., Kostan, J., Janata, J., & Kutejova, E. (2014) · Acta Crystallographica Section D: Biological Crystallography · doi:10.1107/s139900471303397x · Cited by 14
Emerging roles of low-molecular-weight thiols at the host–microbe interface
Dumitrescu, D. G., & Hatzios, S. K. (2023) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2023.102322 · Cited by 14 · cited 1× · see citing works
“Besides their role in maintaining the cellular redox balance, LMW thiols are increasingly recognized for their involvement in various cellular processes, including virulence regulation, host-microbe interactions, and generation of bioactive by-products after their degradation [45].”
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Sulfur-Containing Amino Acids: The Conversion Process from Product to Substrate
Zheng, P.-N., Jin, Y., Wei, C., & Xia, C.-Y. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27114771 · Cited by 2
“Following its role as a methyl donor, SAM is converted into SAH, a potent feedback inhibitor of most methyltransferases [113].”
- Authors
- Hammerstad, M., Steinvik, E., & Hersleth, H.-P.
- Affiliations
- University of Oslo (NO)
- Corresponding author
- Hammerstad, Marta
- Hersleth, Hans-Petter
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2025-12
- Volume
- 88
- Pages
- 103937
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC12719100
- OpenAlex
- W4416411157
- Cited by
- 1
- References
- 72
- Citations by year
- 2026: 1
- FWCI
- 0.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Research Council of Norway (301584)
- Universitetet i Oslo
- European Synchrotron Radiation Facility
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- bacillithiol, SAM-dependent methyltransferase, Chlorobium tepidum, crystal structure, cap domain, substrate specificity, low molecular weight thiols, phylogenetic distribution, molecular docking
- MeSH terms
- Bacterial Proteins, Cysteine, Glucosamine, Methylation, Methyltransferases, Models, Molecular, Molecular Weight, S-Adenosylmethionine, Substrate Specificity, Sulfhydryl Compounds, Crystallography, X-Ray, Catalytic Domain, Molecular Docking Simulation
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