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Chemical Structure| 85-61-0 Chemical Structure| 85-61-0

Structure of Coenzyme A
CAS No.: 85-61-0

Chemical Structure| 85-61-0

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Coenzyme A is a coenzyme that plays an important role in the synthesis and oxidation of fatty acids.

Synonyms: CoA

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Al-Hilfi, Aimen ; Li, Zhen ; Merz Jr, Kenneth M ; Walker, Kevin D ;

Abstract: A Taxus baccatin III:3-amino-3-phenylpropanoyltransferase (BAPT, Accession: AY082804) in clade 6 of the BAHD family catalyzed a Mg2+-dependent transfer of isoserines from their corresponding CoA thioesters. An advanced taxane baccatin III on the biosynthetic pathway in Taxus plants was incubated BAPT and phenylisoserine CoA or isobutenylisoserinyl CoA with and without MgCl2. BAPT biocatalytically converted baccatin III to its 13-O-phenylisoserinyl and 3-(1',1'-dimethylvinyl)isoserinyl analogs, an activity that abrogated when Mg2+ ions were omitted. Baccatin III analogs that are precursors to new generation taxanes were also assayed with BAPT, the Mg2+ cofactor, and 3-(1',1'-dimethylvinyl)isoserinyl CoA to make derivatives at kcat/KM ranging between 27 and 234 s−1 M−1. Molecular dynamics simulations of the BAPT active site modeled on the crystal structure of a BAHD family member (PDB: 4G0B) suggest that Mg2+ causes BAPT to use an unconventional active site space compared to those of other BAHD catalysts, studied over the last 25 years, that use a conserved catalytic histidine residue that is glycine in BAPT. The simulated six-membered Mg2+−coordination complex includes an interaction that disrupts an intramolecular hydrogen bond between the C13-hydroxyl and the carbonyl oxygen of the C4-acetate of baccatin III. A simulation snapshot captured an active site conformation showing the liberated C13-hydroxyl of baccatin III poised for acylation by BAPT through a potential substrate-assisted mechanism.

Keywords: new-generation taxanes ; BAHD biocatalysis ; molecular dynamics ; Mg2+-dependence ; paclitaxel

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Aimen Al-Hilfi ; Zhen Li ; Kenneth M. Merz Jr. ; Irosha N. Nawarathne ; Kevin D. Walker ;

Abstract: A taxane 2-O-benzoyltransferase (mTBT, derived from Accession: AF297618) biocatalyzed the dearoylation and rearoylation of next-generation taxane precursors of drugs effective against multidrug-resistant cancer cells. Various taxanes bearing an acyl, hydroxyl, or oxo group at C13 were screened to assess their turnover by mTBT catalysis. The 13-oxotaxanes were the most productive, where 2-O-debenzoylation of 13-oxobaccatin III was turned over faster compared to 13-oxo-10-O-(n-propanoyl)-10-O-deacetylbaccatin III and 13-oxo-10-O-(cyclopropane carbonyl)-10-O-deacetylbaccatin III, yielding ~20 mg of each. mTBT catalysis was likely affected by an intramolecular hydrogen bond with the C13−hydroxyl. Oxidation to the 13-oxo recovered catalysis. The experimental data for the debenzoylation reaction was supported by Gaussian-accelerated molecular dynamics simulations that evaluated the conformational changes caused by different functional groups at C13 of the substrate. These findings also helped postulate where the 2-O-benzoylation reaction occurs on the paclitaxel pathway in nature. mTBT rearoylated the debenzoylated 13-oxobaccatin III acceptors fastest with a non-natural 3-fluorobenzoyl CoA among the other aroyl CoA thioesters evaluated, yielding ~10 mg of each with excellent regioselectivity at laboratory scale. Reducing the 13-oxo group to a hydroxyl yielded key modified baccatin III precursors (~10 mg at laboratory scale) of new-generation taxoids.

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Product Details of Coenzyme A

CAS No. :85-61-0
Formula : C21H36N7O16P3S
M.W : 767.53
SMILES Code : O[C@H]1[C@](N2C=3C(N=C2)=C(N)N=CN3)(O[C@H](COP(OP(OCC([C@H](C(NCCC(NCCS)=O)=O)O)(C)C)(=O)O)(=O)O)[C@H]1OP(=O)(O)O)[H]
Synonyms :
CoA
MDL No. :MFCD24368566

Safety of Coenzyme A

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Description
Coenzyme A (CoASH) serves as an omnipresent and indispensable cofactor, functioning as a carrier of acyl groups and an activator of carbonyl groups within the citric acid cycle and fatty acid metabolism. It assumes a pivotal role in the oxidation of pyruvate within the citric acid cycle and the metabolic pathways involving carboxylic acids, encompassing short- and long-chain fatty acids[1].

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.30mL

0.26mL

0.13mL

6.51mL

1.30mL

0.65mL

13.03mL

2.61mL

1.30mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

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