pe
pep-05573 v1 CC-BY-SA-4.0

Nisin antimicrobial peptide

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

statusbioassayed targetANTIMICROBIAL length57 aa refs1
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 · 0 verified on platform
prediction metrics boltz-2 2.2.1
ipTM0.000
pTM0.214
avg pLDDT42.3
ranking score0.381
STRUCTURE · PEP-05573 × ANTIMICROBIAL
ranking0.381
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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
sequence57 aa
151015202530354045505557
MSTKDFNLDLVSVSKKDSG ASPRITSISLCTPGCKTGA LMGCAAATATCHCSIHVSK
in the news 6 articles
Hypotheses3 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

Can tweaking one flexible hinge in a natural antibiotic shift how it kills bacteria, and could that make resistance harder to develop?

Many bacteria become resistant to antibiotics by fortifying their membranes. If this variant kills mainly by blocking a building block bacteria need to survive (rather than tearing open their membrane), those membrane-based defenses might not work against it, potentially giving doctors a longer-lasting tool against hard-to-treat infections.

The hypothesis
This nisin variant retains bactericidal activity against Gram-positive pathogens primarily through Lipid II sequestration rather than pore formation, because the hinge alteration in the ITSISLCTPGC region decouples the N-terminal Lipid II-binding domain from the C-terminal pore-forming domain.
Why it’s plausible
In native nisin A, the hinge (NMK) is flexible and allows the C-terminal pore-forming rings D-E (encoded by ATATCHCSIHVSK in this sequence) to reorient toward the membrane after Lipid II is bound. Mutations in the hinge can stiffen or alter the interdomain angle, preventing the C-terminal domain from threading into the bilayer. Sequestration of Lipid II alone is bactericidal (it blocks peptidoglycan synthesis) even without pore formation. The dissociation between agar diffusion improvement and unchanged or worsened MIC in hinge variants reported by the reference is consistent with a shift toward sequestration-dominant killing, since diffusion activity measures zone of inhibition (growth arrest = sequestration sufficient) while MIC kinetics require rapid membrane depolarisation.
Why it matters
A nisin variant that kills primarily by Lipid II sequestration rather than pore formation would be less susceptible to resistance mechanisms that thicken the membrane or alter membrane potential, broadening the therapeutic window.
Plausibility.47
Novelty.33
Impact.60
Basis · grounding2 papers · 1 computed/note
[1]
paper
Hinge variants show enhanced agar diffusion but some show reduced broth MIC, implying different killing mechanisms under the two assay conditions
doi: 10.1371/journal.pone.0079563
[2]
paper
The N-terminal receptor-binding domain and C-terminal pore-forming domain are functionally separable in nisin
doi: 10.1016/j.peptides.2003.09.013
[3]
sequenceC-terminal ATATCHCSIHVSK retains the cysteine residues for D-E ring formation, so pore-forming capacity is structurally present but hinge flexibility determines whether it is deployed
openupdated 2026-06-05

Could a modified version of a food-safe antibiotic be applied to implant surfaces to prevent the stubborn bacterial films that cause so many device-related infections?

Infections on implanted devices like pins and catheters are notoriously hard to treat and often require removing the device entirely. If this variant can kill those bacteria at doses safe for skin cells, it could become a surface coating that protects patients without needing systemic antibiotics, which would be a meaningful option for a problem that currently has very few good solutions.

The hypothesis
This nisin variant is active against biofilm-embedded Staphylococcus epidermidis on implanted medical device surfaces at concentrations below its cytotoxic threshold for human keratinocytes, making it a candidate topical coating agent for transcutaneous devices such as percutaneous pins and subcutaneous implants.
Why it’s plausible
S. epidermidis biofilm on implanted devices is a leading cause of device-associated infections, and Lipid II-targeting mechanisms are effective against slow-growing cells in biofilms because Lipid II availability, not growth rate, is the limiting factor. Nisin has documented oral mucosal and skin application context (10.1016/j.archoralbio.2017.03.017). The MSTKDFNLDLVSVSKKDSG leader sequence region is cleaved post-translationally, yielding a mature peptide. The selectivity axis hit (10.1016/j.peptides.2003.09.013) describes the two-domain architecture as relevant to how nisin interacts with membranes of varying composition. S. epidermidis biofilm matrices are thinner and less negatively charged than those of S. aureus, meaning the Lipid-II-sequestration-dominant mechanism of this hinge variant would be particularly well-suited to this pathogen.
Why it matters
Device-associated S. epidermidis infections lack good targeted treatment options that preserve device function. A nisin hinge variant formulated as a surface coating would address a large unmet clinical need without requiring systemic administration, sidestepping the oral bioavailability limitation.
Plausibility.37
Novelty.43
Impact.62
Basis · grounding2 papers · 1 computed/note
[1]
sourceNisin has potential roles against bacterial pathogens in mucosal surfaces, supporting local-application therapeutic development
[2]
paper
Delivery systems and formulation strategies for antimicrobial peptides including surface coatings are an established field
doi: 10.1016/j.ijpharm.2017.04.082
[3]
paper
Hinge variants retain or exceed nisin A activity against Lactococcus lactis HP, a close relative of staphylococci in membrane architecture
doi: 10.1371/journal.pone.0079563
openupdated 2026-06-05

Does the precise arrangement of certain amino acids in one region of this antibiotic control the three-dimensional shape that lets it latch onto and disable bacteria?

If researchers can pinpoint which specific positions in this region are critical for the antibiotic to fold into the right shape, it could make designing new and improved antibiotics much faster and cheaper, reducing the need for expensive trial-and-error lab work. This kind of map would be a practical tool for anyone working on next-generation antimicrobials.

The hypothesis
The serine and threonine residues within the ITSISLCTPGC stretch of this variant serve as lantibiotic enzyme (NisB/NisC) substrates for dehydration and cyclisation, and their specific arrangement determines whether the resulting lanthionine ring geometry adopts a conformation that enhances or reduces binding to Lipid II compared to wild-type nisin A.
Why it’s plausible
In nisin biosynthesis, NisB dehydrates Ser and Thr to dehydroalanine and dehydrobutyrine respectively, and NisC cyclises them with downstream cysteines. The sequence ITSISLCTPGC contains Thr, Ser, and Cys residues that are substrates for this two-enzyme system. The exact positional arrangement of Ser/Thr relative to Cys determines ring size (lanthionine vs. methyllanthionine) and ring geometry, which directly affects Lipid II contact surface. Altering these residues in the hinge-proximal region, as done in the mutagenesis study, changes which rings form and their three-dimensional shape, with downstream consequences for Lipid II binding affinity.
Why it matters
Understanding which Ser/Thr positions in the hinge-proximal region are critical for correct ring formation would enable a predictive model for lantibiotic engineering, reducing the need for exhaustive mutagenesis screens.
Plausibility.40
Novelty.20
Impact.40
Basis · grounding2 papers · 1 computed/note
[1]
sequenceITSISLCTPGC contains T, S, S, C residues at defined spacing compatible with NisB/NisC substrate requirements for lanthionine ring formation
[2]
paper
Mutagenesis of the hinge produces variants with different activity profiles, consistent with altered post-translational modification patterns
doi: 10.1371/journal.pone.0079563
[3]
paper
The receptor-binding domain of nisin depends on the intact lanthionine ring structure of the N-terminal rings A-C
doi: 10.1016/j.peptides.2003.09.013
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.3809323310852051 boltz-2
3-letter notation
Met-Ser-Thr-Lys-Asp-Phe-Asn-Leu-Asp-Leu-Val-Ser-Val-Ser-Lys-Lys-Asp-Ser-Gly-Ala-Ser-Pro-Arg-Ile-Thr-Ser-Ile-Ser-Leu-Cys-Thr-Pro-Gly-Cys-Lys-Thr-Gly-Ala-Leu-Met-Gly-Cys-Ala-Ala-Ala-Thr-Ala-Thr-Cys-His-Cys-Ser-Ile-His-Val-Ser-Lys
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). Nisin antimicrobial peptide (pep-05573, v1). PeptideModel. https://peptidemodel.com/card/pep-05573
@peptide{pep05573,
  sequence = {MSTKDFNLDLVSVSKKDSGASPRITSISLCTPGCKTGALMGCAAATATCHCSIHVSK},
  target   = {antimicrobial},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 5 by signal overlap
references 1 papers
[1] source scaffold
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