Sulfite reductase (NADPH) (SiR)

Sulfite reductase (SiR) is a complex metalloenzyme that catalyzes the six-electron reduction of sulfite to sulfide, representing a critical step in the assimilatory sulfate reduction pathway (UniProt, 2024). This enzyme is found in plants, fungi, and various bacteria, including pathogens such as Mycobacterium tuberculosis and Salmonella enterica, but is notably absent in the human genome (PubMed, 2022). Because humans lack this pathway and must obtain sulfur-containing amino acids like cysteine and methionine from their diet, SiR is considered a high-priority target for the development of selective antimicrobial and antifungal therapies (NCBI, 2023). The enzyme's architecture typically involves a flavoprotein component and a hemoprotein component containing a unique siroheme-iron-sulfur cluster, which facilitates the challenging multi-electron transfer process (Wikipedia, 2024). Inhibition of SiR leads to the depletion of essential sulfur metabolites, effectively starving the pathogen and inhibiting its growth and virulence. While there are currently no FDA-approved drugs that specifically target sulfite reductase, it remains a focus of drug discovery efforts aimed at addressing antibiotic resistance, particularly in the context of tuberculosis (PubMed, 2021).

Other names

NADPH-sulfite reductaseHydrogen-sulfide:NADP+ oxidoreductaseAssimilatory sulfite reductaseSulfite reductase (ferredoxin)

Inhibition of the enzymatic reduction of sulfite to sulfide, which blocks the de novo biosynthesis of essential sulfur-containing amino acids in microorganisms.