Bacitracin inhibits the reductive activity of protein disulfide isomerase by disulfide bond formation with free cysteines in the substrate‐binding domain
The peptide antibiotic bacitracin is widely used as an inhibitor of protein disulfide isomerase (PDI) to demonstrate the role of the protein-folding catalyst in a variety of molecular pathways. Commercial bacitracin is a mixture of at least 22 structurally related peptides. The inhibitory activity of individual bacitracin analogs on PDI is unknown. For the present study, we purified the major bacitracin analogs, A, B, H, and F, and tested their ability to inhibit the reductive activity of PDI by use of an insulin aggregation assay. All analogs inhibited PDI, but the activity (IC(50) ) ranged from 20 μm for bacitracin F to 1050 μm for bacitracin B. The mechanism of PDI inhibition by bacitracin is unknown. Here, we show, by MALDI-TOF/TOF MS, a direct interaction of bacitracin with PDI, involving disulfide bond formation between an open thiol form of the bacitracin thiazoline ring and cysteines in the substrate-binding domain of PDI.
Pharmacology, Toxicology and Pharmaceutical Science
3
4%
Other
1
1%
Unknown
19
23%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 January 2024.
All research outputs
#12,343,598
of 34,357,314 outputs
Outputs from FEBS Journal
#2,702
of 6,638 outputs
Outputs of similar age
#66,819
of 163,413 outputs
Outputs of similar age from FEBS Journal
#24
of 48 outputs
Altmetric has tracked 34,357,314 research outputs across all sources so far. This one is in the 38th percentile – i.e., 38% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,638 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.8. This one is in the 47th percentile – i.e., 47% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 163,413 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 21st percentile – i.e., 21% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 48 others from the same source and published within six weeks on either side of this one. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.
