Inhibitor Fingerprinting of Rhomboid Proteases by
Activity-Based Protein Profiling Reveals Inhibitor Selectivity and
Rhomboid Autoprocessing
Posted on 2015-10-16 - 00:00
Rhomboid
proteases were discovered almost 15 years ago and are
structurally the best characterized intramembrane proteases. Apart
from the general serine protease inhibitor 3,4-dichloro-isocoumarin
(DCI) and a few crystal structures of the Escherichia coli rhomboid GlpG with other inhibitors, there is surprisingly little
information about inhibitors of rhomboids from other species, probably
because of a lack of general methods to measure inhibition against
different rhomboid species. We here present activity-based protein
profiling (ABPP) as a general method to screen rhomboids for their
activity and inhibition. Using ABPP, we compare the inhibitory capacity
of 50 small molecules against 13 different rhomboids. We find one
new pan rhomboid inhibitor and several inhibitors that display selectivity.
We also demonstrate that inhibition profile and sequence similarity
of rhomboids are not related, which suggests that related rhomboids
may be selectively inhibited. Finally, by making use of the here discovered
inhibitors, we were able to show that two bacterial rhomboids autoprocess
themselves in their N-terminal part.
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Wolf, Eliane
V.; Zeissler, Annett; H. L. Verhelst, Steven (2016). Inhibitor Fingerprinting of Rhomboid Proteases by
Activity-Based Protein Profiling Reveals Inhibitor Selectivity and
Rhomboid Autoprocessing. ACS Publications. Collection. https://doi.org/10.1021/acschembio.5b00514
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AUTHORS (3)
EW
Eliane
V. Wolf
AZ
Annett Zeissler
SH
Steven H. L. Verhelst
KEYWORDS
Inhibitor SelectivityEscherichia coli rhomboid GlpGcrystal structuresDCIRhomboid Proteasesrhomboids autoprocessscreen rhomboidsmeasure inhibitiondisplay selectivityinhibition profilesequence similarityintramembrane proteasesInhibitor FingerprintingABPP15 yearsRhomboid AutoprocessingRhomboid proteasespan rhomboid inhibitorrhomboid species