Perchlorate Reductase Is Distinguished by Active Site Aromatic Gate Residues
Open accessAbstract
Perchlorate is an important ion on both Earth and Mars. Perchlorate reductase (PcrAB), a specialized member of the dimethylsulfoxide reductase superfamily, catalyzes the first step of microbial perchlorate respiration, but little is known about the biochemistry, specificity, structure, and mechanism of PcrAB. Here we characterize the biophysics and phylogeny of this enzyme and report the 1.86-Å resolution PcrAB complex crystal structure. Biochemical analysis revealed a relatively high perchlorate affinity (Km = 6 μm) and a characteristic substrate inhibition compared with the highly similar respiratory nitrate reductase NarGHI, which has a relatively much lower affinity for perchlorate (Km = 1.1 mm) and no substrate inhibition. Structural analysis of oxidized and reduced PcrAB with and without the substrate analog SeO3 (2-) bound to the active site identified key residues in the positively charged and funnel-shaped substrate access tunnel that gated substrate entrance and product release while trapping transiently produced chlorate. The structures suggest gating was associated with shifts of a Phe residue between open and closed conformations plus an Asp residue carboxylate shift between monodentate and bidentate coordination to the active site molybdenum atom. Taken together, structural and mutational analyses of gate residues suggest key roles of these gate residues for substrate entrance and product release. Our combined results provide the first detailed structural insight into the mechanism of biological perchlorate reduction, a critical component of the chlorine redox cycle on Earth.
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The lack of effect of additional electron acceptors may be due to metabolic versatility and differing mechanisms of perchlorate metabolism among species, resulting in inconsistent results.
“However, this may be due to the metabolic versatility and differing mechanisms of perchlorate metabolism among species, resulting in inconsistent results (Youngblut et al., 2016).”
From Simple and effective remediation strategies of Martian perchlorates (2026) · cites this paper as Youngblut et al., 2016
The Comparative Steady-state Kinetics section (page not provided) reports that PcrAB turns over several oxyanions and behaves differently from E. coli nitrate reductase, supporting a limited point about biochemical differences. It does not examine whether additional electron acceptors have no effect or attribute inconsistent results among species to metabolic versatility or differing perchlorate-metabolism mechanisms. (LLM, conf=0.72)
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Cites
Dundas, J., Ouyang, Z., Tseng, J., Binkowski, A., Turpaz, Y., & Liang, J. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl282 · Cited by 1,725 · see citing works
Detection of perchlorate and the soluble chemistry of martian soil at the phoenix lander site
Hecht, M. H., Kounaves, S. P., Quinn, R. C., West, S. J., Young, S. M. M., Ming, D. W., Catling, D. C., Clark, B. C., Boynton, W. V., Hoffman, J., et al. (2009) · Science · doi:10.1126/science.1172466 · Cited by 1,166 · see citing works
Nitrate and periplasmic nitrate reductases
Sparacino-Watkins, C., Stolz, J. F., & Basu, P. (2014) · Chem. Soc. Rev. · doi:10.1039/c3cs60249d · Cited by 426 · cited 1× · see citing works
“Although monodentate and bidentate coordination of Asp to molybdenum atom have been seen in some independent NarGH structures (35, 36, 45), a carboxylate shift has only previously been proposed to protein metals other than molybdenum, such as iron, manganese, cadmium, and zinc (46).”
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- Coates, J. D., and Achenback, L. A. (2006) The microbiology of perchlorate reduction and its bioremediative application, in Perchlorate: Environmen- tal Occurrence, Interactions and Treatment (Gu, B., and Coates, J. D., eds) pp. 279 -295, Springer, New York
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Simple and effective remediation strategies of Martian perchlorates
Coker, H. R., Denvir, A. C., & Howe, J. A. (2026) · Soil Science Society of America Journal · doi:10.1002/saj2.70201 · Cited by 1 · see citing works
- Authors
- Youngblut, M. D., Tsai, C.-L., Clark, I. C., Carlson, H. K., Maglaqui, A. P., Gau-Pan, P. S., Redford, S. A., Wong, A., Tainer, J. A., & Coates, J. D.
- Affiliations
- Energy Biosciences Institute (US)
- Lawrence Berkeley National Laboratory (US)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Coates, John D.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 291
- Issue
- 17
- Pages
- 9190-9202
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4861485
- OpenAlex
- W2295179644
- Cited by
- 88
- References
- 3
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 8 · 2023: 6 · 2022: 5 · 2021: 14 · 2020: 8 · 2019: 12 · 2018: 9 · 2017: 5 · 2016: 3
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (R01GM105404)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chemical Analysis and Environmental Impact
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Keywords
- enzyme active site, substrate inhibition, molybdenum coordination, enzyme crystal structure, Mars
- MeSH terms
- Bacterial Proteins, DNA Helicases, Oxidoreductases, Perchlorates, Catalytic Domain, Rhodocyclaceae
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