Purification and biochemical properties of an N-hydroxyarylamine O-acetyltransferase from Escherichia coli

Yamamura, Ei-Tora; Sayama, Michio; Kakikawa, Makiko; Mori, Masaaki; Taketo, Akira; Kodaira, Ken-Ichi

doi:10.1016/s0304-4165(00)00038-6

Cited by 11 publications

(8 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29,30 The reaction takes place in two separate steps. Initially, acetyl coenzyme A binds to the enzyme and the acetyl moiety is transferred from the cofactor to a cysteine (Cys 68 for the human isoforms) of the protein.…”

Section: Reaction Mechanism and Substrate Specificitymentioning

confidence: 99%

Pharmacogenetics of the arylamine N-acetyltransferases

et al. 2002

View full text Add to dashboard Cite

The arylamine N-acetyltransferases (NATs) are involved in the metabolism of a variety of different compounds that we are exposed to on a daily basis. Many drugs and chemicals found in the environment, such as those in cigarette smoke, car exhaust fumes and in foodstuffs, can be either detoxified by NATs and eliminated from the body or bioactivated to metabolites that have the potential to cause toxicity and/or cancer. NATs have been implicated in some adverse drug reactions and as risk factors for several different types of cancers. As a result, the levels of NATs in the body have important consequences with regard to an individual's susceptibility to certain druginduced toxicities and cancers. This review focuses on recent advances in the molecular genetics of the human NATs.

show abstract

Section: Reaction Mechanism and Substrate Specificitymentioning

confidence: 99%

Pharmacogenetics of the arylamine N-acetyltransferases

et al. 2002

View full text Add to dashboard Cite

show abstract

“…The structural homology observed between these two families, despite limited primary structure homology, has led to the suggestion that other HAT families, including p300/CBP, will have the same protein fold and employ a similar catalytic/ kinetic mechanism (23, 27). There are other acetyltransferases, including acetyl-CoA:arylamine N-acetyltransferase from pigeon liver and N-hydroxyarylamine O-acetyltransferase from Escherichia coli (29,30) that have been demonstrated to employ double displacement (ping-pong) mechanisms. Furthermore, bisubstrate analogues that link acetyl-CoA to 7 or 20 amino acid peptides are poor p300 inhibitors, indirectly arguing against a ternary complex mechanism (31).…”

mentioning

confidence: 99%

Transcriptional Coactivator Protein p300

Thompson¹,

Kurooka²,

Nakatani³

et al. 2001

Journal of Biological Chemistry

121

View full text Add to dashboard Cite

The p300/cAMP response element-binding proteinbinding protein (CBP) family members include human p300 and cAMP response element-binding protein-binding protein, which are both important transcriptional coactivators and histone acetyltransferases. Although the role of these enzymes in transcriptional regulation has been extensively documented, the molecular mechanisms of p300 and CBP histone acetyltransferase catalysis are poorly understood. Herein, we describe the first detailed kinetic characterization of p300 using fulllength purified recombinant enzyme. These studies have employed peptide substrates to systematically examine the substrate specificity requirements and the kinetic mechanism of this enzyme. The importance of nearby positively charged residues in lysine targeting was demonstrated. The strict structural requirement of the lysine side chain was shown. The catalytic mechanism of p300 was shown to follow a ping-pong kinetic pathway and viscosity experiments revealed that product release and/or a conformational change were likely rate-limiting in catalysis. Detailed analysis of the p300 selective inhibitor Lys-CoA showed that it exhibited slow, tight-binding kinetics.Since the initial revelation that yeast Gcn5p (Gcn ϭ global control non-repressed) is a histone acetyltransferase (HAT) 1 (1), and the subsequent determination that a number of other transcriptional co-activators possess HAT activity, there has been an explosion of interest into the role of protein acetylation in vivo (reviewed in Refs. 2-5). More than 20 HATs have now been identified and these have been classified into one of five families (GNAT, MYST (MOZ, YBF2/Sas3, Sas2, Tip60), TAF II 250, nuclear receptor coactivators, and p300/cAMP response element-binding protein-binding protein (CBP)), primarily based upon amino acid sequence homology (2).The p300/CBP family of HATs is represented by two proteins, p300 and CBP, that share considerable sequence homology over their entire length; human p300 and CBP proteins share 91% sequence identity (6). The coactivator p300 is a 2414-amino acid protein that was initially identified as a nuclear binding target of the E1A oncoprotein (7), whereas CBP is 2441 amino acids long and was originally identified as a transcriptional coactivator that bound to phosphorylated cAMP response element-binding protein in mice (8). Subsequently, Arany et al. (6) noted the significant sequence homology between these two proteins and suggested that these two large proteins (ϳ265 kDa) might be functionally equivalent, which has since been confirmed in many cases (9). The protein pair, p300/CBP, as it is now commonly referred to, is important for both cell cycle progression and cellular differentiation and possesses a number of distinct functional domains that have been shown to interact with components of the RNA polymerase II holoenzyme, transcription factors, and nuclear hormone receptors and their co-activators (2, 10 -19) (Fig. 1). Following the determination that p300/CBP-associated factor is a bona fide HAT (2...

show abstract

“…It has been shown that the acetyl-CoA-dependent N-acetylations of aromatic amines proceed via a two-step process involving the transfer of an acetyl group from acetyl-CoA to the enzyme, forming an acetylated enzyme intermediate (step 1), followed by the transfer of an acetyl group from the acetylated enzyme intermediate to aromatic amines (step 2), 16) Thus it is possible to assume that the rapid formation of 4AA2AT in the N-acetylation of 2,4-DAT (Fig. 3) and the greater production of 2,4-DAAT in the N-acetylation of 2AA4AT are due to the higher affinities of 2,4-DAT and 2AA4AT for the acetylated enzyme intermediate.…”

Section: Discussionmentioning

confidence: 99%

Cytosolic Acetyl Transfer and N-Deacetylation Associated with the Metabolism of Carcinogenic 2,4-Diaminotoluene in Rat Liver.

Sayama

Kondo

Mori

2002

JOURNAL OF HEALTH SCIENCE

Self Cite

View full text Add to dashboard Cite

Acetyl transfer and N-deacetylation associated with the metabolism of carcinogenic 2,4-diaminotoluene (2,4-DAT) were examined by detecting the products formed during the incubation of 2,4-DAT and its known urinary metabolites with the liver cytosol fraction from male Wistar rats. Data obtained from the incubation of 4-acetylamino-2-aminotoluene (4AA2AT) with the liver cytosol in the presence of 2,4-diaminobenzoic acid (2,4-DABA) indicated that the cytosol catalyzes the acetyl transfer between 4AA2AT and 2,4-DABA to produce 2,4-DAT and 2-acetylamino-4-aminobenzoic acid (2AA4ABA). The cytosol also catalyzed the acetyl transfer between 2,4-diacetylaminotoluene (2,4-DAAT) and 2,4-DABA to produce 2-acetylamino-4-aminotoluene (2AA4AT) and 2AA4ABA. Without 2,4-DABA, the cytosol catalyzed the N-deacetylations of 4AA2AT and 2,4-DAAT to produce 2,4-DAT and 2AA4AT. 2AA4AT was inactive for both the N-deacetylation and the acetyl transfer. 2,4-DAT itself was N-acetylated to 4AA2AT by incubation with acetyl-CoA, but 2AA4AT and 2,4-DAAT were not detectable in the incubation product. However, both 2AA4AT and 4AA2AT were N-acetylated to 2,4-DAAT by incubation with acetyl-CoA. These findings suggest that 2,4-DAT is reproduced either by the N-deacetylation of 4AA2AT or by the acetyl transfer between 4AA2AT and 2,4-DABA in the metabolism of 2,4-DAT and further suggest that 2,4-DAAT is produced by the acetyl-CoA-dependent N-acetylation of 4AA2AT; 2AA4AT is produced either by the N-deacetylation of 2,4-DAAT or by the acetyl transfer between 2,4-DAAT and 2,4-DABA. Based on these results, the metabolic pathway of 2,4-DAT in the rat is proposed.

show abstract

Purification and biochemical properties of an N-hydroxyarylamine O-acetyltransferase from Escherichia coli

Cited by 11 publications

References 17 publications

Pharmacogenetics of the arylamine N-acetyltransferases

Pharmacogenetics of the arylamine N-acetyltransferases

Transcriptional Coactivator Protein p300

Cytosolic Acetyl Transfer and N-Deacetylation Associated with the Metabolism of Carcinogenic 2,4-Diaminotoluene in Rat Liver.

Contact Info

Product

Resources

About