Peroxisome Proliferator-Activated Receptors (PPARs) May Mediate the Neuroactive Effects of Probiotic Metabolites: An In Silico Approach
Abstract
1. Introduction
2. Results
2.1. Structural Similarity Analysis
2.2. Molecular Targets Selection
2.2.1. Reactome
2.2.2. Interactome
2.2.3. Enrichment, Strength and Validation Analysis of Protein Interactions
2.3. Molecular Docking Studies
2.3.1. Choice of Ligands
2.3.2. Molecular Interaction and Multiple Sequence Alignment
3. Discussion
4. Materials and Methods
4.1. Database, Webpage and Software
4.2. Data Collection
4.2.1. Theoretical Metabolites Collection
4.2.2. Reported Metabolites Collection
4.2.3. Natural Metabolites and Reference Drugs of Target Chosen Collection
4.3. Target Key Molecules
4.3.1. Choice of Ligands
4.3.2. Choice of Target Proteins
4.3.3. Frequency Discrimination
4.3.4. Enrichment Analysis Discrimination
4.4. Docking Analysis
4.4.1. Metabolites, Ligand, and Protein Preparation
4.4.2. Ligand Structure Obtention
4.4.3. Protein Structure Obtention
4.5. Statistical Analysis, Validation and Exclusion Criteria
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Nomenclature
AHR | Aryl Hydrocarbon Receptor |
ADME | Absorption, Distribution, Metabolism, and Excretion |
AF-2 helix | Activation function-2 helix |
Ago | Agonist |
AKT | Protein kinase B |
Ant | Antagonist |
B. animalis | Bifidobacterium animalis spp. lactis |
B. lactis | Bifidobacterium animalis spp. lactis |
BBB | Blood-Brain Barrier |
BioCyc DB | BioCyc Database Collection |
CA | Carbonic anhydrase |
CFU | Colony-forming units |
CID | Compound Identifier (PubChem) |
CNS | Central Nervous System |
DHA | Docosahexaenoic acid, a polyunsaturated fatty acid (PUFA) |
EC | EC Number |
EPA | Eicosapentaenoic acid, a polyunsaturated fatty acid (PUFA) |
FA | Fatty Acids |
FDR | False discovery rate |
FMT | Fecal microbiota transplantation |
GABA | Gamma-aminobutyric acid |
GBA | Gut-Brain Axis |
GIT | Gastrointestinal Tract |
GM | Gut Microbiota |
HGNC | Human Gene Nomenclature Committee |
HIE | Polar histidine |
KB | Ketone Bodies |
LCFAs | Long-Chain Fatty Acids |
LBD | Ligand-binding domain |
L. rhamnosus | Lacticaseibacillus rhamnosus |
MAPK | Mitogen-activated protein kinases |
MCFA | Medium-chain fatty acid |
MUFAs | Monounsaturated Fatty Acids |
NCOA1 | Nuclear Receptor Coactivator 1 |
NOTCH | Eurogenic locus notch homolog protein |
PD | Parkinson Disease |
PubMed DB | PubMed Database |
PXR | Pregnane X Receptor |
PPARs | Peroxisome Proliferator-Activated Receptors |
PPARA | Peroxisome Proliferator-Activated Receptor Alpha |
PPARB/D | Peroxisome Proliferator-Activated Receptor Beta/Delta |
PPARG | Peroxisome Proliferator-Activated Receptor Gamma |
PUFAs | Polyunsaturated Fatty Acids |
RXRA | Retinoid X Receptor Alpha |
RXRB | Retinoid X Receptor Beta |
RXRG | Retinoid X Receptor Gamma |
SDF | Structure Data File |
SMILES | Simplified Molecular Input Line Entry Specification |
SFA | Saturated Fatty Acids |
SCFAs | Short-Chain Fatty Acids |
STP | Swiss Target Prediction |
STRING | Search Tool for the Retrieval of Interacting Genes/Proteins |
TGF | Transforming growth factor beta receptor |
TMAO | Tryptophan metabolites, trimethylamine-N-oxide |
tPSA | Topological polar surface area |
TRPV | Transient receptor potential cation channel subfamily V member |
UNIPROT | Universal Protein Resource |
Wlog P | n-octanol/partition co-efficient water |
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BioCyc | ||||||||
---|---|---|---|---|---|---|---|---|
CID | Trivial Name | PPARA | PPARB | PPARG | RXRA | RXRB | RXRG | |
Limit of 95% percentile | −8.13 | −7.05 | −7.52 | −7.14 | −6.85 | −6.84 | ||
397 | Indole-3-acetamide | −8.22 | −7.61 | −7.97 | −7.98 | −7.83 | ||
995 | Phenanthrene | −7.31 | −8.54 | −8.50 | −8.48 | |||
6780 | Anthraquinone | −7.48 | −8.02 | −8.23 | −8.09 | |||
6986 | P-menthan-3-one | −7.00 | −6.80 | |||||
7108 | Phenothiazine | −7.12 | −8.11 | −8.09 | −7.91 | |||
7460 | Alpha-phellandrene | −7.05 | ||||||
8400 | Benzoin | −7.05 | −7.80 | −7.36 | −7.22 | |||
11142 | Beta-phellandrene | −6.80 | ||||||
26049 | 3-carene | −7.01 | −7.10 | |||||
28649 | Stilbene oxide | −7.10 | −7.13 | −7.25 | ||||
62349 | Menthone lactone | −7.16 | −7.25 | −7.24 | −7.18 | |||
70117 | 3-chlorobenzyl alcohol | −6.94 | ||||||
234817 | Pinoresinol | −8.17 | ||||||
363863 | Maackiain | −7.90 | −7.84 | |||||
439901 | 4′-o-methylisoflavone | −8.25 | −7.33 | −7.73 | −7.10 | |||
445354 | Retinol; vitamin a | −9.02 | −7.99 | −8.18 | −8.13 | |||
494912 | Nsc636229 | −7.55 | −7.55 | −7.01 | ||||
623060 | Medicarpin(p) | −8.06 | −7.06 | |||||
3326923 | Ibuprofen anion | −8.71 | −7.76 | |||||
4055279 | 1-phenylpropan-2-ylazanium | −6.85 | ||||||
5377291 | Hinokiresinol | −7.29 | −7.32 | −6.96 | −7.33 | |||
6440617 | (z)-hinokiresinol | −8.52 | −8.78 | −7.71 | −7.06 | |||
10966551 | 4′-hydroxyisoflavone | −7.63 | −8.05 | −7.81 | −7.33 | −7.86 | ||
25246088 | Cis-12,13-epoxy-9-octadecenoic acid | −7.30 | −7.23 | |||||
77916059 | Noroxomaritidine | −8.48 | −8.62 | −6.92 | ||||
146037227 | Oxomaritinamine | −7.99 | −7.81 | |||||
PubMed | ||||||||
CID | Trivial Name | PPARA | PPARB | PPARG | RXRA | RXRB | RXRG | |
Limit of 95% percentile | −8.12 | −7.13 | −7.17 | −7.28 | −6.94 | −7.00 | ||
322 | 4-trans-4-Hydroxycinnamic acid | −7.29 | ||||||
800 | 2-(1H-indol-3-yl)acetaldehyde | −6.99 | −7.23 | −7.23 | −7.16 | |||
803 | Indole-3-pyruvic acid | −8.79 | −7.82 | −7.24 | −7.05 | −7.01 | ||
1150 | Tryptamine | −8.01 | −7.50 | −7.66 | −7.23 | |||
3744 | 3-Indolepropionic acid | −8.60 | −7.50 | −6.85 | ||||
10394 | 3-(4-Hydroxyphenyl)propionic acid | −7.40 | ||||||
10685 | Tryptophol | −6.98 | −7.10 | |||||
14558 | Indol-3-acrylic acid | −8.26 | −7.07 | −6.89 | ||||
73863 | 3-Indoleglyoxylic acid | −8.02 | −7.40 | −7.10 | −6.92 |
Vit. A | CID | Name | PPARA | PPARB | PPARG | RXRA | RXRB | RXRG | |
---|---|---|---|---|---|---|---|---|---|
1 | 445354-BBB | Retinol | −7.014 | −7.825 | −9.024 | −7.992 | −8.181 | −8.129 | |
2 | 6419707 | Retinoate | −8.453 | −7.825 | −7.543 | −8.310 | −9.383 | −9.680 | |
3 | 638015 | Retinal | −8.021 | −6.080 | −7.497 | −8.913 | −7.593 | −7.880 | |
4 | 449171-BBB | Retinoic acid | −9.790 | −9.700 | −9.509 | ||||
Kb | CID | Name | PPARA | PPARB | PPARG | RXRA | RXRB | RXRG | |
1 | 4071895 | 2-hydroxybutyrate | −6.327 | −5.505 | −5.391 | −5.829 | −5.428 | −5.542 | |
2 | 180 | acetone | −5.023 | −4.554 | −4.615 | −4.373 | −4.389 | −4.490 | |
3 | 6971017 | acetoacetate | −6.571 | −5.395 | −6.229 | −6.382 | −5.711 | −5.823 | |
SCFA | CID | Name | PPARA | PPARB | PPARG | RXRA | RXRB | RXRG | |
1 | 283 | Methanoate (Formiate) | −5.019 | −3.795 | −4.432 | −3.392 | −3.427 | −4.199 | |
2 | 175 | Ethanoate (Acetate) | −5.573 | −4.312 | −4.934 | −5.303 | −4.643 | −4.762 | |
3 | 176 | Ethanoic (Acetic) acid | −5.573 | −4.312 | −4.934 | −5.303 | −4.643 | −4.762 | |
4 | 104745 | Propanoate | −4.115 | −2.710 | −3.432 | −4.449 | −3.204 | −4.131 | |
5 | 1032-BBB | Propanoic (Propionic) acid | −4.112 | −2.708 | −3.430 | −4.447 | −3.202 | −4.129 | |
6 | 264-BBB | Butanoic (Butyric) acid | −6.320 | −5.000 | −5.590 | −6.094 | −5.576 | −5.670 | |
7 | 7991-BBB | Pentanoic (Valeric) acid | −5.633 | −4.942 | −4.846 | −5.577 | −4.631 | −5.271 | |
8 | 8892-BBB | Hexanoic acid (Caproic acid) | −5.126 | −3.836 | −4.998 | −5.347 | −4.956 | −4.486 | |
MCFA | CID | Name | PPARA | PPARB | PPARG | RXRA | RXRB | RXRG | |
1 | 119389-BBB | Octanoate (Caprylate) | −5.318 | −3.839 | −4.974 | −5.415 | −4.839 | −5.405 | |
2 | 379-BBB | Octanoic (caprylic) acid | −5.315 | −3.836 | −4.971 | −5.412 | −4.836 | −5.402 | |
3 | 8158-BBB | Nonanoic (pelargonic) acid | −5.559 | −4.129 | −3.245 | −5.725 | −4.448 | −5.551 | |
4 | 2969-BBB | Decanoic (capric) acid | −2.473 | −1.548 | −3.480 | −3.678 | −3.478 | −3.765 | |
5 | 4149208-BBB | Dodecanoate (laurate) | −2.521 | −2.652 | −1.423 | −4.770 | −3.904 | −4.077 | |
LCFA | CID | Name | PPARA | PPARB | PPARG | RXRA | RXRB | RXRG | |
1 | 11005-BBB | Tetradecanoic (Myristic) acid | −2.847 | −1.169 | −1.731 | −4.993 | −4.607 | −4.769 | |
2 | 13849-BBB | pentadecanoic acid | −2.991 | −1.823 | −1.844 | −5.786 | −5.031 | −5.088 | |
3 | 504166-BBB | Hexadecanoate (Palmitate) | −3.578 | −2.276 | −1.883 | −5.878 | −5.398 | −5.662 | |
4 | 985-BBB | Hexadecanoic (Palmitic acid) | −3.575 | −2.273 | −1.880 | −5.875 | −5.395 | −5.659 | |
5 | 10465-BBB | Heptadecanoic acid | −4.241 | −2.703 | −2.175 | −6.517 | −6.103 | −6.162 | |
6 | 3033836 | Octadecanoate (Stearate) | −3.581 | −3.511 | −2.928 | −3.219 | −1.485 | −2.856 | |
7 | 5281 | Octadecanoic (Stearic) acid | −3.578 | −3.508 | −2.925 | −3.216 | −1.482 | −2.853 | |
8 | 12591 | Nonadecanoic acid | −3.937 | −1.175 | −2.888 | −3.040 | −1.611 | −2.890 | |
MUFA | CID | Name | PPARA | PPARB | PPARG | RXRA | RXRB | RXRG | |
1 | 19499-BBB | but-2-enoic acid | −4.408 | −3.736 | −4.482 | −4.874 | −4.560 | −4.792 | |
2 | 19499-BBB | but-2-enoic acid | −4.126 | −3.308 | −3.926 | −4.709 | −3.794 | −3.850 | |
3 | 151007-BBB | dodec-5-enoic acid | −5.090 | −2.392 | −4.630 | −4.986 | −4.335 | −4.942 | |
4 | 151007-BBB | (Z)-dodec-5-enoic acid (Lauroleinic acid) | −3.088 | −2.366 | −1.959 | −4.607 | −4.275 | −4.506 | |
5 | 5461012-BBB | (Z)-hexadec-9-enoate (Palmitoleate) | −3.621 | −2.500 | −2.775 | −5.762 | −5.211 | −6.290 | |
6 | 4668-BBB | hexadec-9-enoic acid | −4.056 | −2.681 | −2.772 | −6.277 | −5.741 | −5.630 | |
7 | 4668-BBB | hexadec-9-enoic acid (Palmitoleic acid) | −3.618 | −2.497 | −2.538 | −5.759 | −5.208 | −6.287 | |
8 | 5461069 | (Z)-octadec-11-enoate (Vaccenate) | −4.755 | −2.254 | −3.408 | −6.545 | −6.377 | −6.270 | |
9 | 5460221-BBB | (Z)-octadec-9-enoate (Oleate) | −4.130 | −3.831 | −2.946 | −3.632 | −3.445 | −6.620 | |
10 | 12745 | octadec-10-enoic acid | −4.334 | −2.947 | −3.766 | −7.002 | −5.919 | −5.977 | |
11 | 12745 | octadec-10-enoic acid (cis-10-Oleic acid) | −3.945 | −2.531 | −3.234 | −6.013 | −5.900 | −4.571 | |
12 | 965 | octadec-9-enoic acid | −4.777 | −3.983 | −2.943 | −6.762 | −3.442 | −6.617 | |
13 | 965 | octadec-9-enoic acid (cis-9-Oleic acid) | −4.127 | −3.828 | −3.848 | −3.629 | −6.084 | −6.617 | |
PUFA | CID | Name | PPARA | PPARB | PPARG | RXRA | RXRB | RXRG | |
1 | 3931-BBB | (9Z,12Z)-octadeca-9,12-dienoic acid (Linoleic acid) | −5.805 | −3.795 | −6.315 | −7.147 | −6.515 | −6.805 | |
2 | 3931-BBB | octadeca-9,12-dienoic acid | −5.435 | −3.479 | −5.907 | −7.089 | −6.513 | −6.43 | |
3 | 3931-BBB | octadeca-9,12-dienoic acid | −5.342 | −2.787 | −5.761 | −7.02 | −6.476 | −6.394 | |
4 | 3931-BBB | octadeca-9,12-dienoic acid | −5.141 | −2.386 | −3.474 | −6.558 | −6.263 | −6.364 | |
5 | 860-BBB | octadeca-9,12,15-trienoic acid | −6.388 | −4.839 | −6.407 | −7.015 | −6.713 | −6.859 | |
6 | 860-BBB | octadeca-9,12,15-trienoic acid | −5.267 | −4.74 | −6.128 | −7.001 | −6.539 | −6.804 | |
7 | 860-BBB | octadeca-9,12,15-trienoic acid | −5.123 | −4.262 | −3.892 | −6.772 | −6.51 | −6.712 | |
8 | 860-BBB | octadeca-9,12,15-trienoic acid | −4.992 | −4.247 | −3.867 | −6.74 | −6.301 | −6.548 | |
9 | 860-BBB | octadeca-9,12,15-trienoic acid | −4.992 | −4.16 | −3.307 | −6.62 | −5.864 | −6.526 | |
10 | 860-BBB | (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid (alpha-Linolenic acid) | −4.973 | −4.129 | −3.286 | −6.501 | −5.773 | −6.265 | |
11 | 860-BBB | octadeca-9,12,15-trienoic acid | −4.786 | −2.834 | −3.028 | −6.173 | −5.633 | −6.028 | |
12 | 860-BBB | octadeca-9,12,15-trienoic acid | −4.58 | −2.706 | −3.001 | −3.615 | −4.045 | −5.125 | |
445580 | (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid (DHA) | −7.014 | −7.416 | −8.724 | −8.746 | −9.264 | −9.512 | ||
446284 | (5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentaenoic acid (EPA) | −8.815 | −7.433 | −6.911 | −8.441 | −6.812 | −7.845 | ||
PubMed | |||||||||
Indole | CID | Name | PPARA | PPARB | PPARG | RXRA | RXRB | RXRG | |
1 | 798-BBB | indole | −5.934 | −5.692 | −5.840 | −6.131 | −6.164 | −6.177 | |
2 | 10256-BBB | 1H-indole-3-carbaldehyde | −7.272 | −6.528 | −6.521 | −6.647 | −6.598 | −6.685 | |
3 | 800-BBB | 2-(1H-indol-3-yl)acetaldehyde | −7.715 | −6.991 | −7.035 | −7.227 | −7.234 | −7.160 | |
4 | 1150-BBB | 2-(1H-indol-3-yl)ethanamine | −7.231 | −8.007 | −6.737 | −7.497 | −7.657 | −7.232 | |
5 | 10685-BBB | 2-(1H-indol-3-yl)ethanol | −6.942 | −6.926 | −6.405 | −7.085 | −6.977 | −7.102 | |
6 | 14558-BBB | 3-(1H-indol-3-yl)prop-2-enoic acid | −8.258 | −7.067 | −6.570 | −6.679 | −6.889 | −6.594 | |
7 | 14558-BBB | 3-(1H-indol-3-yl)prop-2-enoic acid | −7.733 | −6.943 | −6.094 | −6.329 | −6.251 | −5.938 | |
8 | 14558-BBB | 3-(1H-indol-3-yl)prop-2-enoic acid | −5.135 | −4.448 | −4.461 | −5.225 | −5.464 | −5.033 | |
9 | 14558-BBB | 3-(1H-indol-3-yl)prop-2-enoic acid | −4.749 | −3.815 | −3.898 | −4.963 | −4.891 | −4.967 | |
10 | 73863-BBB | 2-(1H-indol-3-yl)-2-oxo-acetic acid | −8.016 | −7.400 | −7.097 | −7.119 | −6.917 | −6.937 | |
11 | 3744-BBB | 3-(1H-indol-3-yl)propanoic acid | −8.599 | −7.499 | −6.597 | −6.801 | −6.851 | −6.737 | |
12 | 803-BBB | 3-(1H-indol-3-yl)-2-oxo-propanoic acid | −8.790 | −7.815 | −7.243 | −7.006 | −7.045 | −7.008 | |
13 | 6932058 | 1H-indole-3-carboxylate | −7.624 | −6.243 | −6.505 | −6.643 | −6.749 | −6.465 | |
14 | 801 | 2-(1H-indol-3-yl)acetate (Indolacetate) | −7.827 | −7.306 | −6.719 | −7.047 | −7.065 | −7.283 | |
15 | 3080590 | 2-(2-oxoindolin-3-yl)acetic acid | −7.619 | −6.742 | −7.175 | −7.063 | −7.151 | −6.989 | |
16 | 92904 | 2-hydroxy-3-(1H-indol-3-yl)propanoic acid | −8.578 | −8.014 | −6.787 | −7.225 | −7.066 | −7.210 |
Action | CID | Trivial Name | GIT | BBB | IUPHAR/BPS | DB | PPARA | PPARB | PPARG | RXRA | RXRB | RXRG | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Antagonist (Anta) | 446738 | GW 6471 | Low | No | Yes | No | −8.79 | ||||||
−8.51 | |||||||||||||
−8.35 | |||||||||||||
46233311 | GSK0660 | Low | No | Yes | No | −5.21 | |||||||
−4.87 | |||||||||||||
82146 | Bexarotene | High | No | Yes | Yes | −9.16 | |||||||
445154 | Resveratrol | High | Yes | Yes | Yes | −8.46 | |||||||
−4.53 | |||||||||||||
3033 | Diclofenac | High | Yes | Yes | Yes | −7.75 | |||||||
Agonist (Ago) | 3339 | Fenofibrate | High | Yes | Yes | Yes | −7.82 | ||||||
2796 | Clofibrate | High | Yes | Yes | Yes | −6.50 | |||||||
9864881 | Elafibranor | High | No | Yes | Yes | −6.57 | |||||||
9891946 | L-796449 | Low | No | Yes | No | −9.24 | |||||||
11236126 | Seladelpar | Low | No | Yes | Yes | −8.15 | |||||||
4075 | Mesalamine | High | No | Yes | Yes | −5.83 | |||||||
3715 | Indomethacin | High | Yes | Yes | Yes | −9.25 | |||||||
4829 | Pioglitazone | High | No | Yes | Yes | −8.19 | |||||||
−7.71 | |||||||||||||
−6.71 | |||||||||||||
−5.90 | |||||||||||||
77999 | Rosiglitazone | High | No | Yes | Yes | −8.13 | |||||||
−7.76 | |||||||||||||
−7.37 | |||||||||||||
−7.01 | |||||||||||||
9864881 | Elafibranor | High | No | Yes | Yes | −7.29 | |||||||
Antagonist (Anta) | 1548887 | Sulindac | High | No | Yes | Yes | −8.88 | ||||||
3922 | LG-100268 | High | Yes | Yes | No | −9.43 | |||||||
3922 | LG-100268 | High | Yes | Yes | No | −8.85 | |||||||
3922 | LG-100268 | High | Yes | Yes | No | −8.26 | |||||||
Agonist (Ago) | 25195496 | Fluorobexarotene | High | No | Yes | No | −10.60 | ||||||
Activator | 82146 | Bexarotene | High | No | Yes | Yes | −9.92 | ||||||
82146 | Bexarotene | High | No | Yes | Yes | −10.06 | |||||||
82146 | Bexarotene | High | No | Yes | Yes | −10.22 |
A. Alignment numbering | 26 | 29 | 59 | 62 | 63 | 65 | 66 | 67 | 78 | 85 | 86 | 87 | 88 | 89 | 91 | 95 | 96 | 123 | 126 | 127 | 130 | 139 | 141 | 152 | 156 | 160 | 163 | 164 | 167 | 249 | 253 | 265 | 292 | 273 | |
Residues dock agonist | PPARA | - | - | - | - | - | - | - | - | - | C276 | Q277 | - | - | S280 | - | - | - | Y314 | - | F318 | - | M330 | V332 | - | - | - | I354 | K358 | - | H440 | V444 | - | L460 | Y464 |
PPARB | - | - | - | - | - | - | - | - | - | C285 | Q286 | - | - | T289 | - | - | - | H323 | - | F327 | - | L330 | V341 | - | - | - | I363 | I364 | - | H449 | M453 | - | L469 | Y473 | |
PPARG | - | - | - | - | - | - | - | - | - | C285 | - | - | R288 | S289 | - | - | - | - | L326 | Y327 | L330 | - | L341 | - | - | - | - | - | - | - | - | - | - | - | |
Residues dock antagonist | PPARA | - | - | - | T253 | L254 | A256 | K257 | - | - | - | - | C278 | - | - | E282 | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - |
PPARB | - | - | - | - | - | - | - | - | - | - | - | C287 | - | - | E291 | E295 | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | |
PPARG | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | |
Specific residues | PPARA | - | M220 | E251 | T253 | L254 | A256 | - | L258 | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | L456 | - | - |
PPARB | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | F352 | - | - | - | - | - | - | - | - | - | - | |
PPARG | F226 | - | - | - | - | - | - | - | A278 | - | - | - | - | - | - | - | I296 | - | - | - | - | - | - | - | L356 | F360 | - | - | - | - | - | - | - | - | |
Blood: residue that interact >75% residues; green: residues that dock with antagonist; Red: residues that dock with agonist; yellow: specific PPAR residues that dock with any molecule. | |||||||||||||||||||||||||||||||||||
B. Alignment numbering | 50 | 54 | 88 | 91 | 92 | 95 | 124 | 127 | 128 | 131 | 214 | 217 | 218 | 221 | |||||||||||||||||||||
Agonist | RXRA | I268 | A272 | N306 | L309 | - | F313 | V342 | L345 | F346 | V349 | C432 | H435 | L436 | F439 | ||||||||||||||||||||
RXRB | L339 | A343 | N377 | - | I381 | F384 | V413 | I416 | F417 | V420 | C503 | H506 | L507 | F510 | |||||||||||||||||||||
RXRG | V266 | I269 | N307 | - | L311 | F314 | V343 | L346 | F347 | V350 | C433 | H436 | L437 | F440 | |||||||||||||||||||||
Blood: residue that interact >75% residues; normal: residue that interact >75% residues; green: residues that dock with agonist; red: residues that dock with antagonist; yellow; residues that only appear in one protein isotype. |
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Parra, I.; Carrasco-Carballo, A.; Palafox-Sanchez, V.; Martínez-García, I.; Aguilera, J.; Góngora-Alfaro, J.L.; Aranda-González, I.I.; Tizabi, Y.; Mendieta, L. Peroxisome Proliferator-Activated Receptors (PPARs) May Mediate the Neuroactive Effects of Probiotic Metabolites: An In Silico Approach. Int. J. Mol. Sci. 2025, 26, 4507. https://doi.org/10.3390/ijms26104507
Parra I, Carrasco-Carballo A, Palafox-Sanchez V, Martínez-García I, Aguilera J, Góngora-Alfaro JL, Aranda-González II, Tizabi Y, Mendieta L. Peroxisome Proliferator-Activated Receptors (PPARs) May Mediate the Neuroactive Effects of Probiotic Metabolites: An In Silico Approach. International Journal of Molecular Sciences. 2025; 26(10):4507. https://doi.org/10.3390/ijms26104507
Chicago/Turabian StyleParra, Irving, Alan Carrasco-Carballo, Victoria Palafox-Sanchez, Isabel Martínez-García, José Aguilera, José L. Góngora-Alfaro, Irma Isela Aranda-González, Yousef Tizabi, and Liliana Mendieta. 2025. "Peroxisome Proliferator-Activated Receptors (PPARs) May Mediate the Neuroactive Effects of Probiotic Metabolites: An In Silico Approach" International Journal of Molecular Sciences 26, no. 10: 4507. https://doi.org/10.3390/ijms26104507
APA StyleParra, I., Carrasco-Carballo, A., Palafox-Sanchez, V., Martínez-García, I., Aguilera, J., Góngora-Alfaro, J. L., Aranda-González, I. I., Tizabi, Y., & Mendieta, L. (2025). Peroxisome Proliferator-Activated Receptors (PPARs) May Mediate the Neuroactive Effects of Probiotic Metabolites: An In Silico Approach. International Journal of Molecular Sciences, 26(10), 4507. https://doi.org/10.3390/ijms26104507