Structural specificity of coenzyme a for phosphotransacetylase

Shimizu, Masao; Suzuki, Tadao; Hosokawa, Yasuhiro; Nagase, Osamu; Abiko, Yasushi

doi:10.1016/0304-4165(70)90118-2

Cited by 14 publications

(10 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The essential new feature in the model we propose, the coordination of a metal to the P-C-3 hydroxyl group, provides an explanation for previous biological activity studies on altered coenzyme A molecules [9]. It was observed that the diastereomer with an epimeric pantoic acid segment has only 5.5% of the activity of the natural compound while the P-C-3 keto derivative possesses 37% of the native coenzyme A phosphotransacetylase activity [9].…”

Section: Discussionmentioning

confidence: 64%

“…It was observed that the diastereomer with an epimeric pantoic acid segment has only 5.5% of the activity of the natural compound while the P-C-3 keto derivative possesses 37% of the native coenzyme A phosphotransacetylase activity [9]. Epimerization at P-C-3 will prevent complexation in a molecule with an unaltered adenosine diphosphate conformation because either the carbonyl group or one of the gemdimethyls would be forced into close contact with one of the diphosphate oxygens.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Magnetic resonance studies of the conformation of manganese (II) coenzyme A

Wilson

1979

FEBS Letters

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Magnetic resonance studies of the conformation of manganese (II) coenzyme A

Wilson

1979

FEBS Letters

View full text Add to dashboard Cite

“…To add further support, desulfo‐CoA (10 µ m plasmodial concentration) and l ‐[ 14 C]malate were coinjected. Desulfo‐CoA has been reported to be competitive with CoA in several examples of enzyme‐catalysed reactions (inhibition constants of 2–3 µ m ; [26,27]). If the CoA‐ester of malate was not involved, the analogue should not inhibit PMLA synthesis.…”

Section: Resultsmentioning

confidence: 99%

Is β‐poly(L‐malate) synthesis catalysed by a combination of β‐L‐malyl‐AMP‐ligase and β‐poly(L‐malate) polymerase?

Willibald

Bildl

Lee

et al. 1999

European Journal of Biochemistry

View full text Add to dashboard Cite

b-Poly(l-malate) is supposed to function in the storage and transport of histones, DNA polymerases and other nuclear proteins in the giant syncytical cells (plasmodia) of myxomycetes. Here we report on the biosynthesis of [ 14 C]b-poly(l-malate) from injected l-[ 14 C]malate in the plasmodium of Physarum polycephalum. The effects of KCN, arsenate, adenosine 5 H -(a,b-methylene)triphosphate, adenosine 5 H -(b,g-methylene)triphosphate, guanosine 5 H -(b,g-methylene)triphosphate, desulfo coenzyme A and phenylarsinoxid on b-poly(l-malate) synthesis were studied after their coinjection with l-[ 14 C]malate. The synthesis was not affected by KCN or desulfo coenzyme A, but was blocked by arsenate and adenosine 5 H -(a,b-methylene)triphosphate. The plasmodium lysate catalysed an l-malate-dependent ATP-[ 32 P]pyrophosphate exchange, but was devoid of b-poly(l-malate) synthetic activity under all experimental conditions tested. The results suggested an extramitochondrial synthesis of b-poly(l-malate), involving the polymerization of b-l-malyl-AMP. It is assumed that the lack of synthesis in the lysate is caused by the inactivation of b-poly(l-malate) polymerase involving a cell injury kinase pathway. Because injected guanosine 5 H -(b,g-methylene)triphosphate blocks the synthesis, the injury signal is likely to be GTP dependent.Keywords: malyl-AMP-ligase; Physarum polycephalum; plasmodium; polymalate polymerase; polymalate synthetase.b-Poly(l-malate) (PMLA) is a polyanion with a molecular mass ranging from 5 kDa to several hundred kilodaltons and is produced by the syncytic cell form of myxomycetes ([1] and references therein). It consists of l-malyl units, which are linked by ester bonds between the b-carboxylates. The a-carboxylates are free and ionized at neutral pH. The polymer receives strong interest because of its chemical reactivity, biodegradability and availability from sustainable feedstocks [2]. As an unconventional biopolymer, it seems to have a unique physiological role, which is currently being uncovered for the plasmodium of Physarum polycephalum [3,4]. The plasmodium, which specifically produces PMLA, is a single multinuclear giant cell [1]. The nuclei divide synchronously by closed mitosis [5]. The biochemistry behind the plasmodial status is not understood, but PMLA appears to be involved.Evidence comes from the correlation of growth with PMLA synthesis, the integration of newly synthesized PMLA into nuclei [6], the high nuclear level of PMLA comparable with the levels of histones and DNA, the maintenance of a constant nuclear PMLA content, although production rates vary between wild-type and mutant strains and under different growth conditions [6], the higher order complexes of PMLA with DNA-polymerases, histones and other proteins in the nuclei [3,4,7]. It has been assumed that PMLA functions as a storage and carrier molecule to maintain an even distribution of histones, DNA polymerases and other nuclear proteins in the giant cell [4]. A plasmodium-specific protein, polymalatase, has been identified...

show abstract

“…The results obtained are summarized in Table 1, and permit us to specify the necessary conditions for manifestation of the 'active acetate' substrate properties in the case of acetyl-CoA carboxylase. The significance of the CoA 3'-phosphate group for interaction with different CoA-dependent enzymes varies largely: it is indispensable for phosphotransacetylase from Escherichia coli [15], but has no effect on acetyl-CoA synthetase [9, 161. From Table 1, it follows that rat liver acetyl-CoA carboxylase is also insensitive to the absence of 3'-phosphate in the ribose ring of acetyl-CoA.…”

Section: Resultsmentioning

confidence: 99%

Interaction of acetyl‐CoA fragments with rat liver acetyl‐CoA carboxylase

Rabinkov

Velikodvorskaya

Kopelevich³

et al. 1990

European Journal of Biochemistry

View full text Add to dashboard Cite

The interaction of acetyl-CoA fragments with rat liver acetyl-CoA carboxylase has been studied. Dephosphorylated acetyl-CoA did not actually differ from acetyl-CoA in its substrate properties. Non-nucleotide analogues of the substrate, S-acetylpantatheine and it's 4'-phosphate, also possess substrate properties (V,,, = 1.5% and 15% of the maximal rate value of acetyl-CoA carboxylation, respectively). The nucleotide fragment in the acetyl-CoA molecule produces a marked effect on the thermodynamics of the substrate-enzyme interaction, and is apparently involved in activation and appropriate orientation of the acetyl group in the active site. The better substrate properties of S-acetylpantetheine 4-phosphate and the inhibitory properties of pantetheine 4'-phosphate, compared to the unphosphorylated analogues, evidence an important role of the 5'-P-phosphate of 3'-phosphorylated ADP residue in acetyl-CoA binding to the enzyme.Acetyl-CoA carboxylase catalyzes the first step in the pathway of long-chain fatty acid biosynthesis and plays a critical role in the regulation of this process [l, 21. CoA modulates the enzyme activity in the cell, though binding to the specific kinase of carboxylase [3] and directly activating carboxylase at low concentration [4]. The long-chain acyl-CoA are effective competitive inhibitors of the enzyme which assist in the dissociation of the active polymeric form of the enzyme 151. A CoA precursor, pantethine, has found a wide application as a hypolipidaemic drug [6]. According to our data, the 4'-phosphate of D-pantothenic acid possesses a similar activity. Data are available featuring peculiarities of the interaction of CoA, its analogues and precursors with CoA-dependent enzymes [7 -91. However, no data have been reported yet on the specificity of acetyl-CoA carboxylase toward any CoA precursors. The aim of this work was to study the interaction of acetyl-CoA carboxylase with a successive series of CoA precursors and their S-acetyl derivatives, which would allow the evaluation of the individual contributions of different fragments of the CoA molecule to interaction with the enzyme. MATERIALS AND METHODSThe following reagents were used in the study: ATP, phenylmethylsulphonyl fluoride, EDTA from Serva; tris(hydroxymethyl) aminomethane, dithiothreitol, bovine serum albumin (fraction V), tosyl-2-phenylalaninechloromethane, tosyl-L-lysinechloromethane, D-biotin, CoASH, acetyl-CoA, cyanogen bromide purchased from Sigma; avidin from Biolar (USSR), CI-Sepharose 4B from Pharmacia, potassium Dpantothenate and potassium D-pantothenate 4'-phosphate Synthesis of acetyl-CoA and its precursorsD-Pantetheine 4-phosphate was obtained as described previously [8]. Acetyl-CoA, S-acetylpantetheine, and S-acetylpantetheine 4-phosphate were synthesized by acetylation with acetic anhydride (in the latter two cases, after reducing the corresponding disulfides by NaBH4) [lo]. S-Acetylcysteamine was prepared from 2-mercaptoethylamine hydrochloride and acetyl chloride by the procedure of Foyl et al. 1111. Enzyme p...

show abstract

Structural specificity of coenzyme a for phosphotransacetylase

Cited by 14 publications

References 35 publications

Magnetic resonance studies of the conformation of manganese (II) coenzyme A

Magnetic resonance studies of the conformation of manganese (II) coenzyme A

Is β‐poly(L‐malate) synthesis catalysed by a combination of β‐L‐malyl‐AMP‐ligase and β‐poly(L‐malate) polymerase?

Interaction of acetyl‐CoA fragments with rat liver acetyl‐CoA carboxylase

Contact Info

Product

Resources

About