A new structure-based classification of sulfide:quinone oxidoreductases

Area of Science:

• Biochemistry
• Structural Biology
• Microbiology

Background:

• Sulfide:quinone oxidoreductases (SQRs) are essential membrane-bound flavoproteins.
• SQRs play critical roles in sulfide detoxification, energy conservation, and neurotransmitter homeostasis.
• Previous research has provided limited structural and sequence data for SQRs.

Purpose of the Study:

• To re-evaluate SQR classification based on new structural and sequence data.
• To propose a refined, structure-based classification of the SQR protein family.
• To summarize current knowledge and identify outstanding questions regarding SQRs.

Main Methods:

• Analysis of recently determined X-ray crystal structures of SQRs from Aquifex aeolicus and Acidianus ambivalens.
• Comparison of SQR structures with other sulfide-oxidizing enzymes like flavocytochrome c:sulfide dehydrogenase (FCSD).
• Utilizing an expanding database of SQR-like protein sequences.
• Development of structure-based sequence fingerprints for classification.

Main Results:

• X-ray crystallography revealed significant structural differences in the active sites and flavin adenine dinucleotide binding of SQRs.
• SQRs exhibit conformational variations compared to FCSD.
• A growing number of SQR-like sequences and confirmed SQR activities support further family expansion.
• A new classification subdivides the SQR family into six distinct groups based on structure-based sequence fingerprints.

Conclusions:

• The SQR protein family is more diverse than previously recognized, necessitating a revised classification.
• Structure-based sequence analysis provides robust criteria for subdividing SQRs into six groups.
• Further research on SQRs promises significant discoveries in sulfide metabolism and related biological processes.