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Development of Sulfidogenic Sludge from Marine Sediments and Trichloroethylene Reduction in an Upflow Anaerobic Sludge Blanket Reactor
Published on: October 15, 2015
Structure-activity relationship study shows versatility in substrate specificity for heterodisulfide reductase in
Mahdi Faal Maleki1,2, Joakim Bøgelund Jakobsen2, Eva Danielle Schuiten3
1Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Protein Science : a Publication of the Protein Society
|June 12, 2026
Summary
Heterodisulfide reductase (Hdr) is key for methane production by archaea. Researchers found that Hdr can accept modified substrates, expanding our understanding of its catalytic flexibility.
Area of Science:
- Biochemistry
- Microbiology
- Enzyme kinetics
Background:
- Hydrogenotrophic methanogens are archaea crucial for methane production.
- Heterodisulfide reductase (Hdr) is central to methanogenesis, catalyzing heterodisulfide reduction.
- Hdr typically functions with electron donors like [NiFe]-hydrogenase (HdrMvh).
Purpose of the Study:
- To investigate the substrate specificity of Hdr independently of its native electron donors.
- To explore the molecular determinants of Hdr substrate recognition and catalysis.
- To identify alternative substrates for Hdr activity.
Main Methods:
- Isolated Hdr catalytic properties using an artificial electron donor system.
- Synthesized 18 non-endogenous analogs of the native heterodisulfide substrate.
- Evaluated substrate turnover and inhibitory effects of modified substrates.
Main Results:
- Several non-endogenous disulfides were identified as alternative substrates for Hdr.
- Variations in the coenzyme B moiety and replacement of the coenzyme M sulfonate with carboxylate were tolerated.
- Modifications disrupting charge, chain length, or stereochemistry led to loss of activity or inhibition.
Conclusions:
- Hdr exhibits flexibility in substrate recognition, accepting modified heterodisulfide analogs.
- Specific molecular features, including charge balance and stereochemistry, are critical for Hdr catalysis.
- This study provides insights into the structure-activity relationships of Hdr and its potential for engineered applications.
Keywords:
coenzyme M/coenzyme B analogselectron bifurcationenzyme kineticsheterodisulfide reductasemethane mitigationstructure–activity relationshipsubstrate specificityMore Related Videos
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