Catalytic and inhibitory architecture of comammox ammonia monooxygenase
- 1Southern university of science and technology
Abstract
Complete ammonia oxidizers (comammox) are widespread nitrifiers that can dominate ammonia oxidation in diverse environments by efficiently converting ammonia to nitrate within a single cell, yet the molecular basis distinguishing their ammonia monooxygenase (AMO) from those of canonical bacterial AMO remains unresolved. Here we report cryo-electron microscopy (cryo-EM) structures of AMO from the comammox Nitrospira inopinata (NiAMO) in inhibitor-free and allylthiourea (ATU)-bound states at 2.47 and 2.68 angstrom, respectively. NiAMO displays distinctive auxiliary-subunit organization, copper-site configuration and hydrophobic-channel architecture. Integrative molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations support a methyl-plastoquinol (methyl-PQH2)-coupled, CuD-centric catalytic model, with CuC potentially facilitating quinone redox cycling. N. inopinata exhibited broad susceptibility to several known nitrification inhibitors, and ATU-bound NiAMO structure localized the inhibitor to the CuC-CuD region, accompanied by constriction of the hydrophobic channel, which is consistent with the competitive role of ATU demonstrated in recovery assays. Multi-omics analyses further revealed an energy-limited stress response to ATU, including induction of urea transport and utilization systems. Collectively, these findings define a methyl-PQ-linked catalytic and inhibitor-responsive architecture of comammox AMO and establish a mechanistic framework for lineage-aware management of nitrification in natural and engineered ecosystems.
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BibTeX
@misc{mao2026catalytic,
title = {{Catalytic and inhibitory architecture of comammox ammonia monooxygenase}},
author = {T.-Q. Mao and X. Yang and Z.-C. He and J. Yang and R. Wu and K. M. Y. Leung and S. Li and P. Han and W. Peng and Z. Li},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.748776},
url = {https://www.biorxiv.org/content/10.64898/2026.09.02.748776v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Catalytic and inhibitory architecture of comammox ammonia monooxygenase
AU - T.-Q. Mao
AU - X. Yang
AU - Z.-C. He
AU - J. Yang
AU - R. Wu
AU - K. M. Y. Leung
AU - S. Li
AU - P. Han
AU - W. Peng
AU - Z. Li
PY - 2026
DA - 2026/09/02
PB - bioRxiv
DO - 10.64898/2026.09.02.748776
UR - https://www.biorxiv.org/content/10.64898/2026.09.02.748776v1
AB - Complete ammonia oxidizers (comammox) are widespread nitrifiers that can dominate ammonia oxidation in diverse environments by efficiently converting ammonia to nitrate within a single cell, yet the molecular basis distinguishing their ammonia monooxygenase (AMO) from those of canonical bacterial AMO remains unresolved. Here we report cryo-electron microscopy (cryo-EM) structures of AMO from the comammox Nitrospira inopinata (NiAMO) in inhibitor-free and allylthiourea (ATU)-bound states at 2.47 and 2.68 angstrom, respectively. NiAMO displays distinctive auxiliary-subunit organization, copper-site configuration and hydrophobic-channel architecture. Integrative molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations support a methyl-plastoquinol (methyl-PQH2)-coupled, CuD-centric catalytic model, with CuC potentially facilitating quinone redox cycling. N. inopinata exhibited broad susceptibility to several known nitrification inhibitors, and ATU-bound NiAMO structure localized the inhibitor to the CuC-CuD region, accompanied by constriction of the hydrophobic channel, which is consistent with the competitive role of ATU demonstrated in recovery assays. Multi-omics analyses further revealed an energy-limited stress response to ATU, including induction of urea transport and utilization systems. Collectively, these findings define a methyl-PQ-linked catalytic and inhibitor-responsive architecture of comammox AMO and establish a mechanistic framework for lineage-aware management of nitrification in natural and engineered ecosystems.
ER -