Crystal structure of Escherichia coli type I signal peptidase P84A in complex with lipopeptide antibiotic arylomycin A2
Bibliographic record
Abstract
Type I signal peptidase (SPase I) is an essential membrane-bound enzyme that removes amino-terminal signal peptides from secretory proteins. Owing to its critical role in bacterial viability and its periplasmic accessibility, SPase I has emerged as an attractive target for antibiotic development. Arylomycins, a class of macrocyclic lipohexapeptide natural products, inhibit SPase I by binding to its active site. Previous studies have identified a key resistance determinant—a proline residue at the base of the substrate-binding groove (Pro84 in Escherichia coli SPase I)—which reduces arylomycin affinity. Here, we present the crystal structure of the E. coli SPase I P84A mutant in complex with arylomycin A 2 , revealing that the introduced alanine enables an additional hydrogen bond between the enzyme backbone and the arylomycin N-terminal carbonyl, thus enhancing the affinity for arylomycins. Furthermore, a newly developed preprotein-binding assay utilizing a non-cleavable version of ProOmpA Nuclease A demonstrates that substituting SPase I Pro84 with serine or leucine disrupts substrate recognition, underscoring the delicate balance between inhibitor resistance and substrate processing. These findings reveal that residue Pro84 participates in the interaction between preprotein signal peptides and the E. coli SPase I substrate-binding groove, offering a foundation for designing next-generation arylomycin analogs with improved antibacterial potency.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".