Biosynthesis and turnover of DOPA-containing proteins by human cells

Rodgers, Kenneth J.; Hume, Peter; Dunlop, Rachael A.; Dean, Roger T.

doi:10.1016/j.freeradbiomed.2004.08.009

Cited by 43 publications

(47 citation statements)

References 25 publications

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“…26 In fact, the binding of L-DOPA to tyrosyl and phenylalanyltRNA synthetases has been observed in bacterial and prokaryotic-eukaryotic cells, respectively, 41 including mammalian cells in vitro. [42][43][44] Furthermore, an increased level of protein-incorporated L-DOPA was observed in lymphocyte cell proteins of a Parkinson patient treated with this compound. Thus, the incorporation of this "non-protein" amino acid in proteins of susceptible species can at least be suggested as a mechanism of their toxicity.…”

Section: Effects Of L-dopa In Plantsmentioning

confidence: 99%

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The role of L-DOPA in plants

Soares

Marchiosi

Siqueira-Soares

et al. 2014

Plant Signaling & Behavior

148

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Section: Effects Of L-dopa In Plantsmentioning

confidence: 99%

“…Thus, the incorporation of this "non-protein" amino acid in proteins of susceptible species can at least be suggested as a mechanism of their toxicity. 43 …”

Section: Effects Of L-dopa In Plantsmentioning

confidence: 99%

The role of L-DOPA in plants

Soares

Marchiosi

Siqueira-Soares

et al. 2014

Plant Signaling & Behavior

148

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“…This study further demonstrates that the presence of DOPA in newly synthesized proteins can easily be detected using a sensitive redox-staining procedure that detects catechols like DOPA [14,17]. Synthesis in the presence of DOPA and redox staining thus offers a convenient alternative to the use of antibodies or radiolabelled amino acids for the specific detection and quantification of in vitro-synthesized proteins.…”

Section: Discussionmentioning

confidence: 73%

“…It has recently been shown that DOPA can be incorporated directly from the medium into proteins in cultured mouse [16] and human [17] cells, and that incorporation relies on protein synthesis [16]. If translational (ribosome-mediated) incorporation of DOPA is a distinct possibility, the structural and functional consequences of DOPA incorporation would be important to assess.…”

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confidence: 99%

Translational incorporation of L‐3,4‐dihydroxyphenylalanine into proteins

et al. 2005

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The incorporation of non-natural amino acids opens up the possibility to endow proteins with properties that cannot be attained with the 20 natural amino acids encoded by DNA base triplets. The incorporation of non-natural amino acids can readily be achieved with the natural protein-translational machinery, if the structure of the modified amino acid is closely related to the natural amino acid, so that it can be loaded onto tRNA by one of the natural aminoacyl-tRNA synthetases.A wide range of non-natural amino acids has been incorporated into proteins in this way [1]. In general, the efficiency of incorporation decreases with increasing K M value of the aminoacyl-tRNA synthetase for the respective amino acid. This holds, in particular, for the in vivo incorporation of non-natural amino acids, where a pool of natural amino acids is always present. This problem can be circumvented by the use of auxotrophic strains [1] or cell-free protein production systems derived from nonauxotrophic strains combined with a suitably manipulated medium for protein synthesis [2,3].Recently, high-yield, cell-free protein production systems have become available that allow the synthesis of proteins in quantities sufficient for structural genomics applications [4][5][6][7]. High-level incorporation of seleno-methionine (Se-Met) for X-ray crystallography and fluoro-tryptophan (F-Trp) for NMR has been An Escherichia coli cell-free transcription ⁄ translation system was used to explore the high-level incorporation of l-3,4-dihydroxyphenylalanine (DOPA) into proteins by replacing tyrosine with DOPA in the reaction mixtures. ESI-MS showed specific incorporation of DOPA in place of tyrosine. More than 90% DOPA incorporation at each tyrosine site was achieved, allowing the recording of clean 15 N-HSQC NMR spectra. A redox-staining method specific for DOPA was shown to provide a sensitive and generally applicable method for assessing the cell-free production of proteins. Of four proteins produced in soluble form in the presence of tyrosine, two resulted in insoluble aggregates in the presence of high levels of DOPA. DOPA has been found in human proteins, often in association with various disease states that implicate protein aggregation and ⁄ or misfolding. Our results suggest that misfolded and aggregated proteins may result, in principle, from ribosome-mediated misincorporation of intracellular DOPA accumulated due to oxidative stress. High-yield cell-free protein expression systems are uniquely suited to obtain rapid information on solubility and aggregation of nascent polypeptide chains.Abbreviations DOPA, L-3,4-dihydroxyphenylalanine; GFP, cycle 3 mutant green fluorescent protein; hCypA, human cyclophilin A; His 6 -PpiB, N-terminal His 6 -tagged PpiB; HMP, Escherichia coli flavohaemoglobin; HSQC, heteronuclear single-quantum coherence; NBT, nitroblue tetrazolium; PpiB, E. coli peptidyl-prolyl cis-trans isomerase B; RNAP, RNA polymerase; TyrRS, tyrosyl-tRNA synthetase.

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“…L-dopa itself is a natural cellular constituent and a dopamine precursor, but its levels are very low compared to tyrosine levels. Recently, it has been reported that under conditions where the ratio L-dopa/tyrosine is increased, like in the treatment of PD [85], L-dopa is able to be incorporated in proteins instead of tyrosine [86,87]. The increase of L-dopa COMT is involved in estrogen metabolism that has obvious sex related differences [2].…”

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confidence: 99%

Sex-dependent compensated oxidative stress in the mouse liver upon deletion of catechol O-methyltransferase

Tenorio-Laranga¹,

Männistö²,

Karayiorgou³

et al. 2009

Biochemical Pharmacology

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. Sex-dependent compensated oxidative stress in the mouse liver upon deletion of catechol O-methyltransferase. Biochemical Pharmacology, Elsevier, 2009, 77 (9) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 50 A c c e p t e d M a n u s c r i p

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Biosynthesis and turnover of DOPA-containing proteins by human cells

Cited by 43 publications

References 25 publications

The role of L-DOPA in plants

The role of L-DOPA in plants

Translational incorporation of L‐3,4‐dihydroxyphenylalanine into proteins

Sex-dependent compensated oxidative stress in the mouse liver upon deletion of catechol O-methyltransferase

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