pe
pep-05536 v1 CC-BY-SA-4.0

Enterocin-HF antimicrobial peptide

A naturally occurring antimicrobial peptide that kills or stops the growth of bacteria and other microbes; used only as a lab research tool.

statuscomputed targetANTIMICROBIAL length58 aa refs2
antimicrobial
EARLY ENTRY This candidate is newly indexed — supporting evidence is still being added. Have a paper or data point? Contribute below.
status 2 / 5 · 2 contributors
prediction metrics boltz-2 2.2.1
ipTM0.000
pTM0.298
avg pLDDT50.7
ranking score0.465
STRUCTURE · PEP-05536 × ANTIMICROBIAL
ranking0.465
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RECEPTOR UNKNOWN
peptide conformation only · no target structure
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
sequence58 aa
151015202530354045505558
MKKLTSKEMAQVVGGKYYGN GVSCNKKGCSVDWGKAIGII GNNSAANLATGGAAGWKS
in the news 6 articles
Hypotheses5 directions▾ collapse

Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.

openupdated 2026-06-05

Does Enterocin-HF latch onto a particular structure on the bacterial surface, or does it just punch holes at random?

If it turns out to dock on a specific protein gate that common food-borne and hospital pathogens rely on, researchers would know exactly what to optimize for. That could make it far easier to design more potent or selective versions for food preservation or infection control.

The hypothesis
Enterocin-HF binds the IIC and IID subunits of the mannose phosphotransferase system (Man-PTS) on Gram-positive bacteria as its primary membrane receptor, analogous to other class IIa bacteriocins.
Why it’s plausible
The sequence contains the canonical class IIa YGNGV motif (residues ~15-19: YYGNGVSC) and the two-cysteine disulfide in the N-terminal domain (C23 and C29), plus the hydrophobic C-terminal helix-forming region KAIGIIGN. All structurally characterized class IIa bacteriocins whose mechanism has been resolved (pediocin PA-1, sakacin P, leucocin A) exert activity by binding Man-PTS IIC/IID. The card currently lists no target, leaving this association unconfirmed for Enterocin-HF specifically.
Why it matters
Confirming Man-PTS as the receptor would anchor all downstream structure-activity work and explain the selectivity for Listeria and other Gram-positive pathogens that express high Man-PTS levels.
Plausibility.85
Novelty.25
Impact.80
Basis · grounding1 paper · 1 computed/note
[1]
paper
Enterocin CRL35, whose N-terminal region shares high similarity with this peptide, is grouped with mundticin KS as class IIa bacteriocins; class IIa mode of action is membrane permeabilization via receptor docking.
doi: 10.1128/aac.48.7.2778-2781.2004
[2]
sequenceYYGNGVSC motif and disulfide-forming cysteines C23/C29 are the hallmark class IIa structural signature; KAIGIIGN forms the predicted amphipathic C-terminal helix that inserts into lipid bilayers after receptor engagement.
openupdated 2026-06-05

Does breaking one molecular link in this peptide turn a bacteria-killing agent into a merely bacteria-slowing one?

If this holds, it could give researchers a way to tune the peptide for the job at hand. A bacteria-slowing version might be safer for use near human tissue, while the intact form would be kept for situations where outright elimination matters.

The hypothesis
The disulfide bond formed between C23 and C29 in Enterocin-HF is essential for membrane pore formation activity, such that a reduced (open-chain) form of the peptide loses bactericidal activity despite retaining bacteriostatic potency.
Why it’s plausible
The sequence contains `VSCNKKGCS` where the two cysteines are six residues apart, a spacing consistent with a beta-turn-constrained disulfide seen in pediocin-like bacteriocins. Structural studies on pediocin PA-1 and carnobacteriocin B2 show the disulfide locks the N-terminal beta-sheet required for receptor engagement, but the C-terminal hydrophobic region can still insert membranes in a disordered way under reducing conditions with lower efficiency. This predicts a dissociation between static inhibition (membrane insertion) and cidal activity (organized pore formation requiring receptor docking via intact disulfide).
Why it matters
Distinguishing cidal from static modes and linking them to disulfide integrity would guide derivatization strategies: a reduced analog could serve as a bacteriostatic with lower cytotoxicity risk, while the oxidized form targets eradication.
Plausibility.52
Novelty.53
Impact.57
Basis · grounding1 paper · 1 computed/note
[1]
sequenceC23 and C29 are the only cysteines in the 58-aa sequence, spacing and flanking residues match the class IIa disulfide geometry; N-terminal YGNGV precedes the disulfide, C-terminal KAIGIIGN follows it.
[2]
paper
Activity assays on related enterocin CRL35 show time-kill and MIC data are not always concordant, consistent with separable static/cidal mechanisms.
doi: 10.1128/aac.48.7.2778-2781.2004
openupdated 2026-06-05

Could this peptide work against the dangerous drug-resistant bacteria that colonize hospital patients and that current antibiotics often cannot touch?

Vancomycin-resistant Enterococcus is a serious hospital threat with very few treatment options. If this peptide could clear it from the gut at doses the intestine naturally tolerates, it might offer a path to decolonizing high-risk patients without adding to the antibiotic resistance problem.

The hypothesis
Enterocin-HF is active against vancomycin-resistant Enterococcus (VRE) clinical isolates at concentrations below those achievable in the intestinal lumen, making it a candidate for gut-targeted decolonization therapy in VRE-colonized patients.
Why it’s plausible
The clinical-translation axis hits cite a study explicitly designing antimicrobial peptides against VRE. Enterocin-HF is produced by Enterococcus spp., which share cell-envelope composition with Enterococcus target organisms. Class IIa bacteriocins with the same structural scaffold have been shown to act against Gram-positive pathogens including enterococci. The Man-PTS receptor is expressed in Enterococcus, suggesting molecular plausibility for activity. Furthermore, the gastrointestinal tract is a natural production niche for Lactobacillales/Enterococcaceae bacteriocins, so local concentrations needed for activity are potentially achievable without systemic administration.
Why it matters
VRE hospital-acquired infections have very limited treatment options; a non-antibiotic, gut-targeted peptide that acts via membrane disruption rather than cell-wall synthesis would not cross-select for existing vancomycin or linezolid resistance mechanisms.
Plausibility.50
Novelty.42
Impact.73
Basis · grounding2 papers
[1]
paper
Clinical-translation axis hit: study aimed at designing AMP-based anti-VRE agents, confirming the therapeutic gap and mechanism rationale.
doi: 10.1021/jm500960s
[2]
paper
Nanomolar-range activity of related enterocin CRL35 suggests that class IIa bacteriocins including Enterocin-HF can be potent enough for relevant therapeutic concentrations.
doi: 10.1128/aac.48.7.2778-2781.2004
openupdated 2026-06-05

Could changing just two components of this peptide reduce the risk of harming human cells while leaving it just as deadly to bacteria?

Many natural antimicrobial peptides are too toxic to human cells at useful doses. If this swap works as predicted, it would point toward a cleaner, safer version of the peptide, and would help scientists understand which part of its activity is precise and which part is crude collateral damage.

The hypothesis
Replacing the positively charged cluster KK at positions 25-26 (within VSCNKKGCS) with a neutral or negatively charged pair (NN or EE) will reduce electrostatic-driven selectivity for anionic bacterial membranes without eliminating Man-PTS receptor docking, uncoupling receptor-mediated activity from non-specific membrane disruption.
Why it’s plausible
The sequence contains a KK doublet embedded within the disulfide loop (VSCNKKGCS). In class IIa bacteriocins, cationic residues in this loop are proposed to contribute both to initial membrane adsorption via electrostatic attraction to lipoteichoic acids and to receptor contact. If KK primarily mediates electrostatic adsorption, its neutralization should preserve receptor-specific cidal activity while reducing non-selective membrane permeabilization that contributes to hemolysis and cytotoxicity at higher concentrations. This would be a way to engineer a safer, more receptor-selective variant.
Why it matters
Separating receptor-driven from electrostatic-driven membrane activity is a core challenge in AMP optimization for therapeutic use; this specific variant would clarify which mode of action dominates and guide a safety-enhancing engineering path.
Plausibility.45
Novelty.55
Impact.57
Basis · grounding1 paper · 1 computed/note
[1]
sequenceKK at positions 25-26 is flanked by cysteines forming the disulfide loop: VSCNKKGCS; this is an unusually basic patch within a constrained loop, distinct from the diffuse cationic charge of many membrane-disrupting AMPs.
[2]
paper
Selectivity axis hit notes that class IIa bacteriocins are cationic AMPs whose selectivity involves both receptor binding and membrane charge complementarity, suggesting these two contributions can be dissected.
doi: 10.1007/s002030050678
openupdated 2026-06-05

Would this peptide kill the Listeria that makes people sick while leaving a closely related but harmless species unaffected?

Listeria monocytogenes causes serious foodborne illness, but not all Listeria strains are dangerous. If Enterocin-HF could reliably distinguish between them based on a single protein they do or do not carry, it would serve both as a precise food-safety tool and as confirmation that the peptide works through the expected mechanism.

The hypothesis
Enterocin-HF has selective bactericidal activity against Listeria monocytogenes but not against Listeria innocua strains that naturally lack functional Man-PTS IIC/IID subunits, providing a species-level selectivity test for the Man-PTS dependency.
Why it’s plausible
Class IIa bacteriocins show a well-documented pattern where Listeria innocua strains deficient in Man-PTS activity are resistant while L. monocytogenes strains with intact Man-PTS are sensitive. The close homology of Enterocin-HF to mundticin KS (cited via the mundticin L paper, 10.1128/aem.00752-09) predicts the same receptor dependency. If selectivity mirrors mundticin KS, differential activity across Listeria species would be explained entirely by Man-PTS subunit expression, not by differences in membrane composition.
Why it matters
Establishing this selectivity pattern would confirm that Enterocin-HF can be used as a molecular probe to identify Man-PTS expression status in clinical Listeria isolates, and would validate targeting of L. monocytogenes in food-safety or clinical applications.
Plausibility.52
Novelty.35
Impact.53
Basis · grounding1 paper · 1 computed/note
[1]
paper
Mundticin L, a class IIa bacteriocin from E. mundtii, shows narrow Listeria-selective activity consistent with Man-PTS receptor specificity.
doi: 10.1128/aem.00752-09
[2]
sequenceThe YGNGV plus disulfide motif is conserved with mundticin KS and CRL35 suggesting shared receptor-binding residues and therefore shared selectivity profile.
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.4648950695991516 boltz-2
3-letter notation
Met-Lys-Lys-Leu-Thr-Ser-Lys-Glu-Met-Ala-Gln-Val-Val-Gly-Gly-Lys-Tyr-Tyr-Gly-Asn-Gly-Val-Ser-Cys-Asn-Lys-Lys-Gly-Cys-Ser-Val-Asp-Trp-Gly-Lys-Ala-Ile-Gly-Ile-Ile-Gly-Asn-Asn-Ser-Ala-Ala-Asn-Leu-Ala-Thr-Gly-Gly-Ala-Ala-Gly-Trp-Lys-Ser
recipeboltz-2 2.2.1
parametervalue
modelboltz-2 2.2.1
weights
hardwarevast_v100_32gb
mlx version
python
random seed1
msa strategynone_monomer
runtime
predicted by
predicted at2026-05-23
citationbibtex
peptidemodel (2026). Enterocin-HF antimicrobial peptide (pep-05536, v1). PeptideModel. https://peptidemodel.com/card/pep-05536
@peptide{pep05536,
  sequence = {MKKLTSKEMAQVVGGKYYGNGVSCNKKGCSVDWGKAIGIIGNNSAANLATGGAAGWKS},
  target   = {antimicrobial},
  author   = {peptidemodel},
  year     = {2026},
  status   = {computed}
}
related peptides 3 by signal overlap
references 2 papers
[1] source scaffold
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