Target intelligence / Profile preview

AAA-ATPase Drg1 (Drg1)

Target: Drg1
Molecular classification: Enzyme, AAA+ ATPase (ATPases Associated with diverse cellular Activities), Ribosome assembly factor

Overview

AAA-ATPase Drg1 is a cytoplasmic type II AAA+ ATPase essential for the maturation of the large ribosomal subunit (60S) in eukaryotes. It functions by binding to cytoplasmic pre-60S particles and, using ATP hydrolysis, releases specific shuttling assembly factors like Rlp24 to allow ribosome maturation to proceed. Drg1 forms hexameric complexes and undergoes conformational changes during its ATPase cycle, which are essential for its mechanical protein-remodeling activity. It is structurally and functionally related to other AAA+ ATPases such as Cdc48 (p97/VCP). Inhibition of Drg1 (e.g., by diazaborine) blocks ribosome formation and can be lethal to yeast and fungi, making it an attractive antifungal drug target

Other names: Drg1 ATPaseRibosome assembly AAA-ATPase Drg1D1 ring protein Drg1Yeast Drg1 (specifically in *Saccharomyces cerevisiae*)

Mechanism of action

ATPase inhibition (drugs like diazaborine covalently modify Drg1, locking it in an inactive conformation, and thereby block ribosome maturation)

Biological functions

Ribosome biogenesisRelease of shuttling proteins from pre-60S ribosomal particlesInitiation of cytoplasmic maturation of the large ribosomal subunitATP-dependent protein remodeling

Disease associations

Infection (notably as an antifungal target due to its essential role in fungal ribosome assembly)Potential role in resistance and cell viability in fungi

Safety considerations

Selectivity: AAA-ATPase Drg1 shares mechanistic similarities with human AAA-ATPases (e.g., p97/VCP), so selectivity is essential to minimize off-target effects.Essentiality: Complete inhibition in host (human) cells could have deleterious effects if cross-reactivity is high. Currently, the antifungal activity is prioritized due to divergence between yeast/fungal Drg1 and human proteins.

Interacting drugs

Diazaborine

1 more in the full profile.

Biomarkers

No established clinical biomarkers; target engagement can be monitored by disruption of ribosome assembly or ribosomal protein maturation in research settings

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