Regulator of CO metabolism

Regulator of CO metabolism 1
Identifiers
OrganismParaburkholderia xenovorans
SymbolrcoM1
OrthologsOMA: entry
UniProtQ13YL3
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StructuresSwiss-model
DomainsInterPro
Regulator of CO metabolism 2
Identifiers
OrganismParaburkholderia xenovorans
SymbolrcoM2
OrthologsOMA: entry
UniProtQ13IY4
Search for
StructuresSwiss-model
DomainsInterPro

Regulator of CO Metabolism (RcoM) is a heme-containing transcription factor found in bacteria that senses carbon monoxide (CO). In the presence of carbon monoxide, this protein upregulates expression of genes involved in carbon monoxide oxidation or carbon monoxide stress response.[1] RcoM is functionally related to another heme-containing transcription factor, CooA, but RcoM shares no structural relationship with CooA.[2]

Structure

RcoM is composed of an N-terminal Per-Arnt-Sim PAS domain, which contains an Fe(II) heme cofactor, and a C-terminal DNA-binding LytTR domain. CO binding by the PAS domain is very high affinity (~10−10 M−1) and elicits changes in DNA-binding activity, the nature of which is not fully known.[2][3]

Mechanism

RcoM proteins are single-component, heme-based transcription factors that combine an N-terminal PAS heme-sensor domain with a C-terminal LytTR DNA-binding domain. The PAS domain binds a single molecule of heme, while the LytTR domain recognizes triplet direct-repeat motifs upstream of carbon monoxide (CO) oxidation genes within the cox regulon.[4][2]

RcoM homologs, including those from Paraburkholderia xenovorans, function as homodimers.[2] In the ferrous Fe(II) state, RcoM-1 proteins typically coordinate heme with a histidine and a methionine ligand; CO replaces the methionine ligand and binds directly to the heme, activating the protein for high-affinity DNA binding.[5]

RcoM paralogs differ in ligand coordination and CO-responsive behavior. RcoM-1 acts as a low-CO “accumulating” switch with histidine/methionine heme ligation and relatively low-affinity DNA binding, whereas RcoM-2 is a cysteine-ligated hemoprotein that undergoes a redox-mediated ligand switch, resulting in high-affinity CO binding and enhanced DNA recognition in the CO-bound state.[6][7][8][9] Both paralogs regulate microbial CO metabolism genes, particularly under conditions of persistent CO exposure.

Potential therapeutic applications

A genetically engineered RcoM truncate has been prepared that acts as a high affinity carbon monoxide sequestration agent with high selectivity over oxygen. This engineered RcoM could potentially be used to treat carbon monoxide poisoning.[10]

References

  1. ↑ Kerby RL, Youn H, Roberts GP (May 2008). "RcoM: a new single-component transcriptional regulator of CO metabolism in bacteria". Journal of Bacteriology. 190 (9): 3336–3343. doi:10.1128/JB.00033-08. PMC 2347395. PMID 18326575.
  2. 1 2 3 4 Dent MR, Roberts MG, Bowman HE, Weaver BR, McCaslin DR, Burstyn JN (April 2022). "Quaternary Structure and Deoxyribonucleic Acid-Binding Properties of the Heme-Dependent, CO-Sensing Transcriptional Regulator PxRcoM". Biochemistry. 61 (8): 678–688. doi:10.1021/acs.biochem.2c00086. PMC 11155679. PMID 35394749. S2CID 248049748.
  3. ↑ Bouzhir-Sima L, Motterlini R, Gross J, Vos MH, Liebl U (October 2016). "Unusual Dynamics of Ligand Binding to the Heme Domain of the Bacterial CO Sensor Protein RcoM-2". The Journal of Physical Chemistry B. 120 (41): 10686–10694. Bibcode:2016JPCB..12010686B. doi:10.1021/acs.jpcb.6b08160. PMID 27661620.
  4. ↑ Kerby RL, Roberts GP (November 2012). "Burkholderia xenovorans RcoM(Bx)-1, a transcriptional regulator system for sensing low and persistent levels of carbon monoxide". Journal of Bacteriology. 194 (21): 5803–5816. doi:10.1128/JB.01024-12. PMC 3486110. PMID 22923594.
  5. ↑ Bowman HE, Dent MR, Burstyn JN (July 2016). "Met(104) is the CO-replaceable ligand at Fe(II) heme in the CO-sensing transcription factor BxRcoM-1". Journal of Biological Inorganic Chemistry. 21 (4): 559–569. doi:10.1007/s00775-016-1368-5. PMID 27283195. S2CID 17330386.
  6. ↑ Marvin KA, Kerby RL, Youn H, Roberts GP, Burstyn JN (August 2008). "The transcription regulator RcoM-2 from Burkholderia xenovorans is a cysteine-ligated hemoprotein that undergoes a redox-mediated ligand switch". Biochemistry. 47 (34): 9016–28. doi:10.1021/bi800486x. PMC 2849662. PMID 18672900.
  7. ↑ Vos MH, Salman M, Liebl U (2022). "Early processes in heme-based CO-sensing proteins". Frontiers in Molecular Biosciences. 9 1046412. doi:10.3389/fmolb.2022.1046412. PMC 9670170. PMID 36406263.
  8. ↑ Durante-Rodríguez G, de Francisco-Polanco S, García JL, Díaz E (August 2024). "Characterization of a MHYT domain-coupled transcriptional regulator that responds to carbon monoxide". Nucleic Acids Research. 52 (15): 8849–8860. doi:10.1093/nar/gkae575. PMC 11347149. PMID 38966994.
  9. ↑ Dent MR, Weaver BR, Roberts MG, Burstyn JN (May 2023). "Carbon Monoxide-Sensing Transcription Factors: Regulators of Microbial Carbon Monoxide Oxidation Pathway Gene Expression". Journal of Bacteriology. 205 (5) e00332-22: e0033222. doi:10.1128/jb.00332-22. PMC 10210986. PMID 37154694.
  10. ↑ Dent MR, DeMartino AW, Xu Q, Chen X, Gandhi A, Hwang HS, et al. (August 2025). "Engineering a highly selective, hemoprotein-based scavenger as a carbon monoxide poisoning antidote with no hypertensive effect". Proceedings of the National Academy of Sciences of the United States of America. 122 (32) e2501389122. doi:10.1073/pnas.2501389122. PMC 12358919. PMID 40763026. Lay summary in: Garcia de Jesús E (29 August 2025). "A bioengineered protein may someday treat carbon monoxide poisoning". Science News.
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