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Chemoproteomics reveals disruption of metal homeostasis and metalloproteins by the antibiotic holomycin

ABSTRACT: The natural product holomycin contains a unique cyclic disulfide and exhibits broad-spectrum antimicrobial activities. Reduced holomycin chelates metal ions with high affinity and disrupts metal homeostasis in the cell. To identify cellular metalloproteins that are affected by holomycin, reactive-cysteine profiling was performed using isotopic Tandem Orthogonal Proteolysis–Activity-based Protein Profiling. This chemoproteomic analysis showed that holomycin treatment increases the reactivity of metal-coordinating cysteine residues in several zinc-dependent and iron-sulfur cluster-dependent enzymes. Whole-proteome abundance analysis revealed that holomycin treatment induces zinc starvation, iron starvation, and cellular stress. This study sets the stage for investigating the impact of metal-binding molecules on metalloproteomes using chemoproteomics.

INSTRUMENT(S): LTQ Orbitrap XL, LTQ Orbitrap Discovery

ORGANISM(S): Escherichia Coli

TISSUE(S): Cell Culture

SUBMITTER: Julia Falco

LAB HEAD: Eranthie Weerapana

PROVIDER: PXD040777 | Pride | 2023-08-14

REPOSITORIES: Pride

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			Action	DRS
	DTASelect-filter_Ecoli_holomycin_0x_H_2x_L_1_heavy.txt	Txt
	DTASelect-filter_Ecoli_holomycin_0x_H_2x_L_1_light.txt	Txt
	DTASelect-filter_Ecoli_holomycin_0x_H_2x_L_2_heavy.txt	Txt
	DTASelect-filter_Ecoli_holomycin_0x_H_2x_L_2_light.txt	Txt
	DTASelect-filter_Ecoli_holomycin_0x_H_2x_L_3_heavy.txt	Txt

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