Cryo-EM Structure of <i>Salmonella typhimurium</i> ArnC; the Key Enzyme in Lipid-A Modification Conferring Polymyxin Resistance
Bibliographic record
Abstract
1 Abstract Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, including Gram-negative ESKAPE pathogens. However, an increasing number of pathogens employ a defense strategy involving a relay of enzymes encoded by the pmrE(ugd) loci and the arnBCDTEF operon. As a result, an Ara-4N headgroup is added to the lipid-A component of outer membrane (OM) lipopolysaccharides (LPS) rendering polymyxins ineffective. Here, we report the cryo-EM structures of glycosyltransferase ArnC from Salmonella typhimurium resolved in both apo and UDP-bound forms at resolutions 2.75 Å and 3.8 Å, respectively. The structure of the ArnC protomer comprises of three distinct regions: an N-terminal glycosyltransferase domain, transmembrane region, and the interface helices (IHs). ArnC forms a stable tetramer with C2 symmetry through interactions in the C-terminal region, which is expected to protrude into the cytosol, where the β8 strand inserts into the adjacent protomer. ArnC protomers have two distinct types of interfaces involving multiple hydrogen bonds and salt bridges. The binding of UDP induces conformational changes that stabilizes structurally labile A-loop, spanning residues 201 to 213, and part of the putative catalytic pocket formed by IH1 and IH2. The comparative analysis of ArnC structures with homologs GtrB and DPMS suggests the key residues involved in ArnC catalytic activity.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".