Aurovertin B
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Basic Info
| Common Name | Aurovertin B(F04995) |
| 2D Structure | |
| Description | Aurovertin B is a mycotoxin and antibiotic produced by the fungus Calcarisporium arbuscula. It is known for its ability to inhibit oxidative phosphorylation. (A3002, A3032) |
| FRCD ID | F04995 |
| CAS Number | 55350-03-3 |
| PubChem CID | 6441012 |
| Formula | C25H32O8 |
| IUPAC Name | [(1S,3S,4S,5S,7R)-7-ethyl-4-hydroxy-3-[(1E,3E,5E)-6-(4-methoxy-3-methyl-6-oxopyran-2-yl)hexa-1,3,5-trienyl]-1,5-dimethyl-2,6-dioxabicyclo[3.2.1]octan-8-yl] acetate |
| InChI Key | QXCOFYWOWZJFEA-UBIXZPEVSA-N |
| InChI | InChI=1S/C25H32O8/c1-7-20-24(4)23(30-16(3)26)25(5,33-20)22(28)18(32-24)13-11-9-8-10-12-17-15(2)19(29-6)14-21(27)31-17/h8-14,18,20,22-23,28H,7H2,1-6H3/b9-8+,12-10+,13-11+/t18-,20+,22-,23?,24-,25-/m0/s1 |
| Canonical SMILES | CCC1C2(C(C(O1)(C(C(O2)C=CC=CC=CC3=C(C(=CC(=O)O3)OC)C)O)C)OC(=O)C)C |
| Isomeric SMILES | CC[C@@H]1[C@]2(C([C@@](O1)([C@H]([C@@H](O2)/C=C/C=C/C=C/C3=C(C(=CC(=O)O3)OC)C)O)C)OC(=O)C)C |
| Synonyms |
Aurovertin-B
aurovertin b
NSC 329699
2H-Pyran-2-one, 6-(6-(8-(acetyloxy)-7-ethyl-4-hydroxy-1,5-dimethyl-2,6-dioxabicyclo(3.2.1)oct-3-yl)-1,3,5-hexatrienyl)-4-methoxy-5-methyl-, (1S-(1-alpha,3-alpha(1E,3E,5E),4-beta,5-alpha-7-beta))-
55350-03-3
SCHEMBL1067574
LS-127419
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organic oxygen compounds |
| Class | Organooxygen compounds |
| Subclass | Carbohydrates and carbohydrate conjugates |
| Intermediate Tree Nodes | Glycosyl compounds |
| Direct Parent | C-glycosyl compounds |
| Alternative Parents |
|
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | C-glycosyl compound - 1,4-dioxepane - Alkyl aryl ether - Pyranone - Dioxepane - Pyran - Oxane - Monosaccharide - Heteroaromatic compound - Vinylogous ester - Tetrahydrofuran - Carboxylic acid ester - Secondary alcohol - Lactone - Oxacycle - Carboxylic acid derivative - Organoheterocyclic compound - Dialkyl ether - Monocarboxylic acid or derivatives - Ether - Alcohol - Hydrocarbon derivative - Organic oxide - Carbonyl group - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as c-glycosyl compounds. These are glycoside in which a sugar group is bonded through one carbon to another group via a C-glycosidic bond. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 460.523 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 8 |
| Complexity | 942 |
| Monoisotopic Mass | 460.21 |
| Exact Mass | 460.21 |
| XLogP | 2.2 |
| Formal Charge | 0 |
| Heavy Atom Count | 33 |
| Defined Atom Stereocenter Count | 5 |
| Undefined Atom Stereocenter Count | 1 |
| Defined Bond Stereocenter Count | 3 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.7751 |
| Human Intestinal Absorption | HIA+ | 0.8020 |
| Caco-2 Permeability | Caco2- | 0.5485 |
| P-glycoprotein Substrate | Substrate | 0.6995 |
| P-glycoprotein Inhibitor | Inhibitor | 0.8416 |
| Non-inhibitor | 0.5094 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8604 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6618 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7568 |
| CYP450 2D6 Substrate | Non-substrate | 0.8718 |
| CYP450 3A4 Substrate | Substrate | 0.5903 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8755 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8281 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9303 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.6936 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.7491 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.7666 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9858 |
| Non-inhibitor | 0.9124 | |
| AMES Toxicity | AMES toxic | 0.5193 |
| Carcinogens | Non-carcinogens | 0.9117 |
| Fish Toxicity | High FHMT | 0.9777 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9992 |
| Honey Bee Toxicity | High HBT | 0.7617 |
| Biodegradation | Not ready biodegradable | 0.9750 |
| Acute Oral Toxicity | II | 0.3791 |
| Carcinogenicity (Three-class) | Danger | 0.4519 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.9971 | LogS |
| Caco-2 Permeability | 0.5823 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 3.4157 | LD50, mol/kg |
| Fish Toxicity | -0.2449 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 1.3551 | pIGC50, ug/L |
Targets
- General Function:
- Transmembrane transporter activity
- Specific Function:
- Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (By similarity).
- Gene Name:
- ATP5A1
- Uniprot ID:
- P25705
- Molecular Weight:
- 59750.06 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
- General Function:
- Transporter activity
- Specific Function:
- Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.
- Gene Name:
- ATP5B
- Uniprot ID:
- P06576
- Molecular Weight:
- 56559.42 Da
- Mechanism of Action:
- Aurovertins are a mixed, noncompetitive inhibitors of both ATP hydrolysis and synthesis. They do this by inhibiting the proton-pumping F1F0-ATP synthase by binding to beta-subunits in its F1 catalytic sector. F1F0-ATP synthase is responsible for the terminal step of oxidative phosphorylation. Each ATP synthase complex has three beta subunits, and aurovertins are believed to bind with varying affinity to two subunits on sites in a cleft between the nucleotide-binding and C-terminal domains, thus preventing closure of the catalytic interfaces necessary for the cyclic interconversion of catalytic sites.
References
- Johnson KM, Swenson L, Opipari AW Jr, Reuter R, Zarrabi N, Fierke CA, Borsch M, Glick GD: Mechanistic basis for differential inhibition of the F1Fo-ATPase by aurovertin. Biopolymers. 2009 Oct;91(10):830-40. doi: 10.1002/bip.21262. [19462418 ]
- General Function:
- Transmembrane transporter activity
- Specific Function:
- Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(1) domain and the central stalk which is part of the complex rotary element. The gamma subunit protrudes into the catalytic domain formed of alpha(3)beta(3). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.
- Gene Name:
- ATP5C1
- Uniprot ID:
- P36542
- Molecular Weight:
- 32995.665 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]