Notes for MYCTU cds1 (O69652)
Gene Summary
- UniProt: O69652 (Reviewed Swiss-Prot)
- Gene: cds1 (Rv3684)
- Protein: L-cysteine desulfhydrase Cds1
- EC: 4.4.1.1
- Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
PANTHER Family
This gene belongs to PANTHER subfamily PTHR10314:SF135 within family PTHR10314.
See family-level analysis: interpro/panther/PTHR10314/PTHR10314-notes.md
Key Finding: IBA Annotation Error
The IBA annotation GO:0019344 (L-cysteine biosynthetic process) is INCORRECT for this gene.
- Reason: SF135 (Cds1 subfamily) performs cysteine CATABOLISM (EC 4.4.1.1), not biosynthesis
- Branch length: 0.528 from root - longest branch, indicating significant functional divergence
- Correct annotations: GO:0019450 (cysteine catabolic process), GO:0080146 (L-cysteine desulfhydrase activity)
| Gene |
UniProt |
Subfamily |
Function |
| cds1 (Rv3684) |
O69652 |
SF135 |
Cysteine DESULFHYDRASE (catabolism) |
| cysK1 (Rv2334) |
P9WP55 |
SF194 |
Cysteine SYNTHASE (biosynthesis) |
| cysM (Rv1336) |
P9WP53 |
SF162 |
Cysteine SYNTHASE (biosynthesis) |
Gene-Specific Notes
Experimental Evidence (PMID:34439535 - Kunota et al. 2021)
- Identified Rv3684 (Cds1) as an H2S-producing enzyme in Mtb
- Δcds1 disruption significantly reduces H2S production in all media tested
- H2S production confirmed using lead acetate assay, BiCl3 assay, and amperometric microsensor
- Products identified by LC-MS/MS: H2S + pyruvate (confirms desulfhydrase activity)
Biochemical Characterization
- Kinetics: KM = 11.26 mM for cysteine, kcat = 78.71 sec-1
- Cofactor: PLP (pyridoxal 5'-phosphate) at Lys67
- Inhibitors: AOAA (PLP inhibitor) - YES; PAG (CGL inhibitor) - NO
- This confirms Cds1 is a true cysteine desulfhydrase, NOT a cystathionine gamma-lyase
Physiological Role
- H2S stimulates respiration via cytochrome bd
- Modulates balance between respiration and glycolysis
- Contributes to redox homeostasis (affects ergothioneine and mycothiol levels)
- Δcds1 shows 40% reduction in basal oxygen consumption rate
- Δcds1 cells grow poorly with 4 mM cysteine (enzyme eliminates toxic cysteine)
- Δcds1 shows increased survival after clofazimine or rifampicin treatment
- H2S may contribute to antibiotic sensitivity
Drug Target Potential
The finding that Δcds1 shows increased antibiotic sensitivity suggests Cds1 could be a drug target for TB treatment in combination with existing antibiotics.
Last updated: 2026-01-06