Probing the active site of homoserine trans‐succinylase
Open accessAbstract
Homoserine trans‐succinylase is the first enzyme in methionine biosynthesis of Escherichia coli and catalyzes the activation of homoserine via a succinylation reaction. The in vivo activity of this enzyme is subject to tight regulation by several mechanisms, including repression and activation of gene expression, feedback inhibition, temperature regulation and proteolysis. This complex regulation reflects the key role of this enzyme in bacterial metabolism. Here, we demonstrate – using proteomics and high‐resolution mass spectrometry – that succinyl is covalently bound to one of the two adjacent lysine residues at positions 45 and 46. Replacing these lysine residues by alanine abolished the enzymatic activity. These findings position the lysine residues, one of which is conserved, at the active site.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Earlier work did not conclusively determine the chemical structure of the lysine modification.
“However, these studies were not sufficient to fully establish the chemical structure of the modification.”
From SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways (2013) · cites this paper as Rosen et al., 2004
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Thompson, J. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.24.4876 · Cited by 39,119 · see citing works
MUTANTS OF ESCHERICHIA COLI REQUIRING METHIONINE OR VITAMIN B 12
Davis, B. D., & Mingioli, E. S. (1950) · Journal of Bacteriology · doi:10.1128/jb.60.1.17-28.1950 · Cited by 2,894 · see citing works
Hanzelka, B. L., & Greenberg, E. P. (1996) · Journal of Bacteriology · doi:10.1128/jb.178.17.5291-5294.1996 · Cited by 150 · see citing works
Val, D. L., & Cronan, J. E. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.10.2644-2651.1998 · Cited by 140 · see citing works
Görg, A., Postel, W., Domscheit, A., & Günther, S. (1988) · Electrophoresis · doi:10.1002/elps.1150091103 · Cited by 121 · see citing works
Shevchenko, A., Chernushevich, I. V., Wilm, M. S., & Mann, M. (2003) · Humana Press eBooks · doi:10.1385/1-59259-045-4:1 · Cited by 112 · see citing works
Methionine Biosynthesis in Enterobacteriaceae: Biochemical, Regulatory, and Evolutionary Aspect
Saint‐Girons, I., Parsot, C., Zakin, M. M., Bârzu, O., Cohen, G. N., & Weissbach, H. (1988) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238809083374 · Cited by 104 · see citing works
Growth Rate of Escherichia coli at Elevated Temperatures: Limitation by Methionine
Ron, E. Z., & Davis, B. D. (1971) · Journal of Bacteriology · doi:10.1128/jb.107.2.391-396.1971 · Cited by 103 · see citing works
Self-citationMaxon, M. E., Redfield, B. G., Cai, X. Y., Shoeman, R. L., Fujita, K., Fisher, W., Stauffer, G. V., Weissbach, H., & Brot, N. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.1.85 · Cited by 97 · see citing works
Protein aggregation in Escherichia coli: role of proteases
Rosen, R., Biran, D., Gur, E., Becher, D., Hecker, M., & Ron, E. Z. (2002) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2002.tb11020.x · Cited by 83 · see citing works
Self-citationMultimetabolite Control of a Biosynthetic Pathway by Sequential Metabolites
Lee, L., Ravel, J. M., & Shive, W. (1966) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)96455-0 · Cited by 72 · see citing works
In vivo aggregation of a single enzyme limits growth of Escherichia coli at elevated temperatures
Gur, E., Biran, D., Gazit, E., & Ron, E. Z. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.03257.x · Cited by 66 · see citing works
Self-citationControl of methionine biosynthesis in Escherichia coli by proteolysis
Biran, D., Gur, E., Gollan, L., & Ron, E. Z. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.02097.x · Cited by 61 · see citing works
Self-citationBorn, T. L., & Blanchard, J. S. (1999) · Biochemistry · doi:10.1021/bi991710o · Cited by 56 · see citing works
Ron, E. Z., & Shani, M. (1971) · Journal of Bacteriology · doi:10.1128/jb.107.2.397-400.1971 · Cited by 56 · see citing works
Self-citationThe role of peptide deformylase in protein biosynthesis: A proteomic study
Bandow, J. E., Becher, D., Büttner, K., Hochgräfe, F., Freiberg, C., Brötz, H., & Hecker, M. (2003) · PROTEOMICS · doi:10.1002/pmic.200390043 · Cited by 49 · see citing works
Self-citationShoeman, R. L., Coleman, T. A., Redfield, B. G., Greene, R. C., Smith, A. A., Saint‐Girons, I., Brot, N., & Weissbach, H. (1985) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(85)90965-9 · Cited by 46 · see citing works
Glycerol-3-phosphate Cytidylyltransferase
Pattridge, K. A., Weber, C. H., Friesen, J. A., Sanker, S., Kent, C., & Ludwig, M. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306174200 · Cited by 45 · see citing works
Heat shock-dependent transcriptional activation of the metA gene of Escherichia coli
Biran, D., Brot, N., Weissbach, H., & Ron, E. Z. (1995) · Journal of Bacteriology · doi:10.1128/jb.177.5.1374-1379.1995 · Cited by 38 · see citing works
Self-citationGrowth rate of Enterobacteriaceae at elevated temperatures: limitation by methionine
Ron, E. Z. (1975) · Journal of Bacteriology · doi:10.1128/jb.124.1.243-246.1975 · Cited by 37 · see citing works
Self-citationNango, E., Eguchi, T., & Kakinuma, S. (2003) · The Journal of Organic Chemistry · doi:10.1021/jo034706y · Cited by 33 · see citing works
The Escherichia coli regulatory protein MetJ binds to a tandemly repeated 8bp palindrome
Davidson, B. E., & Girons, I. S. (1989) · Molecular Microbiology · doi:10.1111/j.1365-2958.1989.tb00149.x · Cited by 28 · see citing works
Ron, E. Z., Alajem, S., Biran, D., & Grossman, N. (1990) · Antonie van Leeuwenhoek · doi:10.1007/bf00548929 · Cited by 24 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Maxon, M.E. et al. (1989) Proc. Natl. Acad. Sci. USA 86, 85-89.
Cited by
Sorted by citations
Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase
Du, J., Zhou, Y., Su, X., Yu, J. J., Khan, S., Jiang, H., Kim, J., Woo, J., Kim, J. H., Choi, B. H., et al. (2011) · Science · doi:10.1126/science.1207861 · Cited by 1,429 · see citing works
The growing landscape of lysine acetylation links metabolism and cell signalling
Choudhary, C., Weinert, B. T., Nishida, Y., Verdin, E., & Mann, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3841 · Cited by 1,324 · see citing works
SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways
Park, J., Chen, Y., Tishkoff, D. X., Peng, C., Tan, M., Dai, L., Xie, Z., Zhang, Y., Zwaans, B. M. M., Skinner, M. E., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.06.001 · Cited by 1,000 · see citing works
Weinert, B. T., Scholz, C. W., Wagner, S., Iešmantavičius, V., Su, D., Daniel, J. A., & Choudhary, C. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.07.024 · Cited by 757 · see citing works
Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies
Wu, X., Xu, M., Geng, M., Chen, S., Little, P. J., Xu, S., & Weng, J. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01439-y · Cited by 290 · see citing works
Protein Lysine Acylation and Cysteine Succination by Intermediates of Energy Metabolism
Lin, H., Su, X., & He, B. (2012) · ACS Chemical Biology · doi:10.1021/cb3001793 · Cited by 236 · see citing works
Li, W., Li, F., Zhang, X., Lin, H., & Xu, C. S. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00825-8 · Cited by 203 · see citing works
Oxidative stress‐triggered interactions between the succinyl‐ and acetyl‐proteomes of rice leaves
Zhou, H., Finkemeier, I., Guan, W., Tossounian, M., Wei, B., Young, D., Huang, J., Messens, J., Yang, X., Zhu, J., et al. (2017) · Plant Cell & Environment · doi:10.1111/pce.13100 · Cited by 125 · see citing works
The dawn of succinylation: a posttranslational modification
Alleyn, M. D., Breitzig, M., Lockey, R. F., & Kolliputi, N. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00148.2017 · Cited by 122 · see citing works
An Epigenetic Role of Mitochondria in Cancer
Liu, Y., Chen, C., Wang, X., Sun, Y., Zhang, J., Chen, J., & Shi, Y. (2022) · Cells · doi:10.3390/cells11162518 · Cited by 125 · see citing works
Hasan, M. M., Yang, S., Zhou, Y., & Mollah, M. N. H. (2015) · Molecular BioSystems · doi:10.1039/c5mb00853k · Cited by 109 · see citing works
Histone succinylation and its function on the nucleosome
Liu, J., Shangguan, Y., Tang, D., & Dai, Y. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16676 · Cited by 87 · see citing works
SuccFind: a novel succinylation sites online prediction tool via enhanced characteristic strategy
Xu, H., Shi, S., Wen, P.-P., & Qiu, J. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv439 · Cited by 64 · see citing works
Xu, Y., Shen, C., Ma, J., Chen, W., Mao, J., Zhou, Y., & Chen, L. (2017) · Scientific Reports · doi:10.1038/s41598-017-02128-x · Cited by 56 · see citing works
Hasan, M. M., Khatun, M. S., Mollah, M. N. H., Yong, C., & Guo, D. (2017) · International Journal of Nanomedicine · doi:10.2147/ijn.s140875 · Cited by 54 · see citing works
Shen, C., Xue, J., Sun, T., Guo, H., Zhang, L., Meng, Y., & Wang, H. (2016) · Scientific Reports · doi:10.1038/srep21764 · Cited by 49 · see citing works
Large-Scale Assessment of Bioinformatics Tools for Lysine Succinylation Sites
Hasan, M. M., Khatun, M. S., & Kurata, H. (2019) · Cells · doi:10.3390/cells8020095 · Cited by 46 · see citing works
Hondorp, E. R., & Matthews, R. G. (2006) · EcoSal Plus · doi:10.1128/ecosalplus.3.6.1.7 · Cited by 45 · see citing works
Xu, J., Xu, Z., Zhou, Y. Q., & Ye, B. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6b00131 · Cited by 43 · see citing works
Feng, S., Jiao, K., Guo, H., Jiang, M., Hao, J., Wang, H., & Shen, C. (2017) · BMC Genomics · doi:10.1186/s12864-017-3978-x · Cited by 43 · see citing works
Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies
Jia, H., Jiang, L., Shen, X., Ye, H., Li, X., Zhang, L., Hu, Y., Song, D., Jia, H., & Wang, Z. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02397-5 · Cited by 48 · see citing works
The Growing Landscape of Succinylation Links Metabolism and Heart Disease
Yang, L., Miao, S., Zhang, J., Wang, P., Liu, G., & Wang, J. (2021) · Epigenomics · doi:10.2217/epi-2020-0273 · Cited by 36 · see citing works
Systematic Analysis of the Lysine Succinylome in Candida albicans
Zheng, H., He, Y., Zhou, X., Qian, G., Lv, G., Shen, Y., Liu, J., Li, D., Li, X., & Liu, W. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6b00578 · Cited by 36 · see citing works
Succinylation and redox status in cancer cells
Dai, X., Zhou, Y., Han, F., & Li, J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1081712 · Cited by 35 · see citing works
Zubieta, C., Arkus, K. A. J., Cahoon, R. E., & Jez, J. M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709283200 · Cited by 33 · see citing works
An emerging field: Post‐translational modification in microbiome
Duan, H., Zhang, X., & Figeys, D. (2022) · PROTEOMICS · doi:10.1002/pmic.202100389 · Cited by 25 · see citing works
Methionine Biosynthesis in Escherichia coli and Corynebacterium glutamicum
Figge, R. M. (2006) · Microbiology monographs · doi:10.1007/7171_2006_059 · Cited by 26 · see citing works
From the genome sequence to the protein inventory of Bacillus subtilis
Becher, D., Büttner, K., Moche, M., Heßling, B., & Hecker, M. (2011) · PROTEOMICS · doi:10.1002/pmic.201100090 · Cited by 24 · see citing works
Self-citationAn Update on Lysine Deacylases Targeting the Expanding “Acylome”
Olsen, C. A. (2013) · ChemMedChem · doi:10.1002/cmdc.201300421 · Cited by 19 · see citing works
Ubiquitination in plant biotic and abiotic stress
Fu, X., Tang, X., Liu, W., Ghimire, S., Zhang, H., Zhang, N., & Si, H. (2023) · Plant Growth Regulation · doi:10.1007/s10725-023-01095-w · Cited by 18 · see citing works
Ziegler, K., Noble, S. M., Mutumanje, E., Bishop, B., Huddler, D. P., & Born, T. L. (2007) · Biochemistry · doi:10.1021/bi0620252 · Cited by 17 · see citing works
Crystal structure of homoserine O‐succinyltransferase from Bacillus cereus at 2.4 Å resolution
Zubieta, C., Krishna, S. S., McMullan, D., Miller, M. D., Abdubek, P., Agarwalla, S., Ambing, E., Astakhova, T., Axelrod, H. L., Carlton, D. D., et al. (2007) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21208 · Cited by 16 · see citing works
Impact of Lysine Succinylation on the Biology of Fungi
Adejor, J., Tumukunde, E., Li, G., Lin, H., Xie, R., & Wang, S. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46020065 · Cited by 11 · see citing works
Su, H., Lou, Y., Fu, Y., Zhang, Y., Liu, N., Liu, Z., Zhou, Y., & Kong, J. (2017) · Scientific Reports · doi:10.1038/s41598-017-14477-8 · Cited by 13 · see citing works
Li, X., Yang, D., Yang, Y., Jin, G., Yin, X., Zheng, Y., Xu, J., & Yang, Y. (2022) · Cells · doi:10.3390/cells11121947 · Cited by 11 · see citing works
Tasmia, S. A., Ahmed, F. F., Mosharaf, P., Hasan, M., & Mollah, N. H. (2021) · Current Genomics · doi:10.2174/1389202922666210219114211 · Cited by 8 · see citing works
The yeast mitochondrial succinylome: Implications for regulation of mitochondrial nucleoids
Frankovský, J., Keresztesová, B., Bellová, J., Kunová, N., Čanigová, N., Hanáková, K., Bauer, J., Ondrovičová, G., Lukáčová, V., Siváková, B., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101155 · Cited by 8 · see citing works
Yang, W., Wu, J., & Cui, G. (2025) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003939 · Cited by 6 · see citing works
Mollah, M. N. H., Tasmia, S. A., Kibria, M. K., Islam, M. A., & Khatun, M. S. (2022) · Current Protein and Peptide Science · doi:10.2174/1389203723666220628121817 · Cited by 6 · see citing works
Coe, D. M., & Viola, R. E. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.03.004 · Cited by 6 · see citing works
Li, S.-H., Zhou, Y.-Q., Xu, Y., Ran, S.-X., Hou, M.-Y., Li, Q.-M., Zhong, X., & Zhong, F. (2022) · Frontiers in Plant Science · doi:10.3389/fpls.2022.1001935 · Cited by 5 · see citing works
He, J., Lai, T., Zhou, Z., Yang, H., Zheng, L., Liu, Z., Li, N., He, Y., Zeng, S., Munai, E., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-09937-5 · Cited by 4 · see citing works
The Prediction of Succinylation Site in Protein by Analyzing Amino Acid Composition
Bui, V.-M., & Nguyen, V. (2016) · Advances in intelligent systems and computing · doi:10.1007/978-3-319-49073-1_67 · Cited by 4 · see citing works
Understanding emerging bioactive metabolites with putative roles in cancer biology
Philips, O., Sultonova, M., Blackmore, B., & Murphy, J. P. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1014748 · Cited by 4 · see citing works
Alsharif, H. (2024) · Biotechnology & Biotechnological Equipment · doi:10.1080/13102818.2024.2425694 · Cited by 2 · see citing works
Shen, C., Yao, X., Zhao, D., & Lu, L. (2021) · European Journal of Horticultural Science · doi:10.17660/ejhs.2021/86.5.10 · Cited by 2 · see citing works
Maurya, B., Colaço, M., Wouters, J., Pochet, L., & Misquith, S. (2021) · Biochimie · doi:10.1016/j.biochi.2021.05.016 · Cited by 2 · see citing works
Protein succinylation in disease: Mechanistic insights and therapeutic targeting
Li, W., & Li, J. (2026) · Genes & Diseases · doi:10.1016/j.gendis.2026.102183 · Cited by 1 · see citing works
Mizrahi, I., Biran, D., Gur, E., & Ron, E. Z. (2007) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2007.03.012 · Cited by 1 · see citing works
Self-citationSIRT5 Reveals Novel Enzymatic Activities of Sirtuins
He, B., & Lin, H. (2016) · Springer eBooks · doi:10.1007/978-94-024-0962-8_6
Introduction to Protein Posttranslational Modifications (PTMs)
Bao, X. (2020) · Springer theses · doi:10.1007/978-981-15-2509-4_1
Systematic Analysis of Lysine Succinylation in Vero cells infected with Small Ruminant MorbillivirusPreprint
Meng, X., Zhu, X., Zhang, R., & Zhang, Z. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.17.444595
Meng, X., Zhu, X., Wang, X., Zhang, R., Zhang, Z., & Sun, Y. (2025) · BMC Veterinary Research · doi:10.1186/s12917-025-04496-3
Histone lysine succinylation: a comprehensive review of enzymatic pathways and disease associations
Zhang, M., Peng, H., Liang, Z., & Gu, J. (2025) · Genome Instability & Disease · doi:10.1007/s42764-025-00148-w
Yang, Y., Yu, Z., Gao, R., Zhang, Y., Zhang, Z., Zhong, X., Jiao, L., Du, K., Wu, Y., Wei, M., et al. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.11.050
Lysine succinylation: a review of its impacts on the reproductive function and related disease
Huang, X., Huang, Y., Lai, J., Wang, Z., Ge, C., Luo, T., Cui, Y., & li, J. (2026) · Reproduction Fertility and Development · doi:10.1071/rd25115 · Cited by 1 · see citing works
- Authors
- Rosen, R., Becher, D., Büttner, K., Biran, D., Hecker, M., & Ron, E. Z.
- Affiliations
- Tel Aviv University (IL)
- Universität Greifswald (DE)
- Corresponding author
- Ron, Eliora Z.
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2004-10-27
- Volume
- 577
- Issue
- 3
- Pages
- 386-392
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2069918331
- Cited by
- 58
- References
- 24
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 9 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 6 · 2016: 5 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- active site, methionine biosynthesis, Escherichia coli, succinylation, lysine residues, enzyme regulation, product inhibition, gene expression regulation, proteolysis, temperature regulation
- MeSH terms
- Acyltransferases, Alanine, Binding Sites, Catalysis, Enzyme Activation, Escherichia coli, Homoserine, Isoelectric Focusing, Lysine, Methionine, Mass Spectrometry, Electrophoresis, Gel, Two-Dimensional, Gene Expression Regulation, Bacterial, Sequence Analysis, DNA, Amino Acid Substitution, Escherichia coli Proteins, Proteomics, Homoserine O-Succinyltransferase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
