T3DB: Aurovertin B

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (3)XML

Targets (3)

Record Information

Version

2.0

Creation Date

2010-05-12 17:30:02 UTC

Update Date

2014-12-24 20:26:29 UTC

Accession Number

T3D3750

Identification

Common Name

Aurovertin B

Class

Small Molecule

Description

Aurovertin B is a mycotoxin and antibiotic produced by the fungus Calcarisporium arbuscula. It is known for its ability to inhibit oxidative phosphorylation. (1, 2)

Compound Type

Ester
Ether
Fungal Toxin
Mycotoxin
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
aurovertin b
Aurovertin b
Aurovertin-B

Chemical Formula

C₂₅H₃₂O₈

Average Molecular Mass

460.517 g/mol

Monoisotopic Mass

460.210 g/mol

CAS Registry Number

55350-03-3

IUPAC Name

7-ethyl-4-hydroxy-3-[6-(4-methoxy-5-methyl-2-oxo-2H-pyran-6-yl)hexa-1,3,5-trien-1-yl]-1,5-dimethyl-2,6-dioxabicyclo[3.2.1]octan-8-yl acetate

Traditional Name

7-ethyl-4-hydroxy-3-[6-(4-methoxy-3-methyl-6-oxopyran-2-yl)hexa-1,3,5-trien-1-yl]-1,5-dimethyl-2,6-dioxabicyclo[3.2.1]octan-8-yl acetate

SMILES

CCC1OC2(C)C(OC(C)=O)C1(C)OC(C=CC=CC=CC1=C(C)C(OC)=CC(=O)O1)C2O

InChI Identifier

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+

InChI Key

InChIKey=QXCOFYWOWZJFEA-YIDQAKLOSA-N

Chemical Taxonomy

Description

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.

Kingdom

Organic compounds

Super Class

Organic oxygen compounds

Class

Organooxygen compounds

Sub Class

Carbohydrates and carbohydrate conjugates

Direct Parent

C-glycosyl compounds

Alternative Parents

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

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.011 g/L	ALOGPS
logP	4.02	ALOGPS
logP	2.55	ChemAxon
logS	-4.6	ALOGPS
pKa (Strongest Acidic)	12.91	ChemAxon
pKa (Strongest Basic)	-3.7	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	6	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	100.52 Å²	ChemAxon
Rotatable Bond Count	8	ChemAxon
Refractivity	125.5 m³·mol⁻¹	ChemAxon
Polarizability	50.32 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03dl-3010900000-c4525159484338b9f17a	2019-02-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-000l-9253500000-de99b6ca162b48fea239	2019-02-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-000i-9000000000-5519cc4c33543249968c	2019-02-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0aor-1001900000-d3c84433ba7bbd118362	2019-02-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0a4l-9313800000-8b0989059edc464ed5ab	2019-02-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4i-9101000000-d7a7ad73181a683f8ffc	2019-02-23	View Spectrum

Toxicity Profile

Route of Exposure

Oral, dermal, inhalation, and parenteral (contaminated drugs). (5)

Mechanism of Toxicity

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. (2, 3, 4)

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Aurovertin B is a mycotoxin and antibiotic produced by the fungus Calcarisporium arbuscula. (1)

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

DB07394

HMDB ID

Not Available

PubChem Compound ID

6441012

ChEMBL ID

Not Available

ChemSpider ID

Not Available

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

Not Available

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

Not Available

General References

Ueno Y: The toxicology of mycotoxins. Crit Rev Toxicol. 1985;14(2):99-132. [3158480 ]
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 ]
van Raaij MJ, Abrahams JP, Leslie AG, Walker JE: The structure of bovine F1-ATPase complexed with the antibiotic inhibitor aurovertin B. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):6913-7. [8692918 ]
Gledhill JR, Walker JE: Inhibitors of the catalytic domain of mitochondrial ATP synthase. Biochem Soc Trans. 2006 Nov;34(Pt 5):989-92. [17052243 ]
Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. ATP synthase subunit beta, mitochondrial

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

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 ]
van Raaij MJ, Abrahams JP, Leslie AG, Walker JE: The structure of bovine F1-ATPase complexed with the antibiotic inhibitor aurovertin B. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):6913-7. [8692918 ]
Gledhill JR, Walker JE: Inhibitors of the catalytic domain of mitochondrial ATP synthase. Biochem Soc Trans. 2006 Nov;34(Pt 5):989-92. [17052243 ]

Target Details

2. ATP synthase subunit alpha, mitochondrial

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 ]

Target Details

3. ATP synthase subunit gamma, mitochondrial

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 ]

Aurovertin B (T3D3750)

Structure for T3D3750: Aurovertin B

Targets

References

References

References