Phenylalanyl-tRNA synthetase from E. coli MRE-600: analysis of the active site distribution on the enzyme subunits by affinity labelling

Ходырева, С. Н.; Moor, Nina; Ankilova, V.N.; Lavrik, Olga I.

doi:10.1016/0167-4838(85)90029-9

Cited by 24 publications

(13 citation statements)

References 16 publications

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“…PheRS is a class II aaRS with an additional ␤-subunit that forms a (␣␤) 2 heterotetramer (7,8). Unlike other class II aaRSs, PheRS aminoacylates the tRNA at the 2Ј-and not the 3Ј-hydroxyl position (9,10).…”

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confidence: 99%

“…Phenylalanine is subsequently transferred to the 3Ј-end of tRNA Phe (11). The larger ␤-subunit PheT (800 residues) mediates the physical interaction with the tRNA Phe molecule and exclusively carries out the editing func- tion of the enzyme by cleaving tRNA molecules that are mischarged with tyrosine (7,8,12). Eukaryotes contain distinct cytosolic and mitochondrial PheRS homologs.…”

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confidence: 99%

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The Role of a Novel Auxiliary Pocket in Bacterial Phenylalanyl-tRNA Synthetase Druggability

Abibi

Ferguson

Fleming

et al. 2014

Journal of Biological Chemistry

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Background: Phenylalanyl-tRNA synthetase inhibitors have been shown to be efficacious in animal models of infection. Results: Inhibitors occupy a newly identified hydrophobic auxiliary binding pocket. Conclusion: Compound binding in this pocket leads to high screening hit rates, resistance frequencies, and elevated plasma protein binding. Significance: New inhibitors may be identified by avoiding the auxiliary pocket.

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confidence: 99%

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confidence: 99%

The Role of a Novel Auxiliary Pocket in Bacterial Phenylalanyl-tRNA Synthetase Druggability

Abibi

Ferguson

Fleming

et al. 2014

Journal of Biological Chemistry

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“…Two subunits of the αβ -heterodimer have no detectable sequence homology. Neither the α - or β -monomers nor the α 2 - or β 2 -dimers manifest catalytic activity of tRNA aminoacylation [10]. The α -subunit of PheRS contains common to class II aaRSs catalytic module (CAM, composed of domains A1 and A2), which together with the N-terminal coiled-coil fragment (CC) is involved in tRNA Phe binding and aminoacylation (Figure 1).…”

Section: Phers: Structural Organization and Evolutionmentioning

confidence: 99%

Structural Aspects of Phenylalanylation and Quality Control in Three Major Forms of Phenylalanyl-tRNA Synthetase

Klipcan

Finarov

Moor

et al. 2010

Journal of Amino Acids

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Aminoacyl-tRNA synthetases (aaRSs) are a canonical set of enzymes that specifically attach corresponding amino acids to their cognate transfer RNAs in the cytoplasm, mitochondria, and nucleus. The aaRSs display great differences in primary sequence, subunit size, and quaternary structure. Existence of three types of phenylalanyl-tRNA synthetase (PheRS)—bacterial (αβ)2, eukaryotic/archaeal cytosolic (αβ)2, and mitochondrial α—is a prominent example of structural diversity within the aaRSs family. Although archaeal/eukaryotic and bacterial PheRSs share common topology of the core domains and the B3/B4 interface, where editing activity of heterotetrameric PheRSs is localized, the detailed investigation of the three-dimensional structures from three kingdoms revealed significant variations in the local design of their synthetic and editing sites. Moreover, as might be expected from structural data eubacterial, Thermus thermophilus and human cytoplasmic PheRSs acquire different patterns of tRNAPhe anticodon recognition.

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“…29,30 Affinity labeling to localize the substrate binding site in Escherichia coli PheRS (ecPheRS) along with crystallographic data of Thermus thermophilus PheRS (ttPheRS) complexed with phenylalanine (Phe) and phenylalaninyl-adenylate (PheOH-AMP), the synthetic analog of phenylalanyl-adenylate (Phe-AMP), corroborate that the α subunit of PheRS on its own is unable to carry out the first step of the aminoacylation reaction. 31,32 Sequence analysis shows that the amino acid binding loop (residues α257-α263 of ttPheRS; TyrPheProPheValGluPro) of α subunit together with the metal-binding loop (residues β450-β465 of ttPheRS; ArgLeuAspLeuArgLeuGluGluAspLeuValGluGluValAspArg) of β subunit are evolutionarily retained among different species and form metal-mediated conserved α/β subunit interface. Conservation of these residues among different PheRS across species implies the importance of the metal-mediated α/β subunit interface in enzymatic activity, especially in the first step of the aminoacylation reaction.…”

Section: Structural Diversity Of Phersmentioning

confidence: 99%

Phenylalanyl-tRNA synthetase

Chakraborty¹,

Banerjee²

2016

RRBC

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Phenylalalnyl-tRNA synthetase (PheRS), a member of class II aminoacyl-tRNA synthetases, catalyzes the synthesis of phenylalanyl-tRNA Phe (Phe-tRNA Phe ). Hence, like other aminoacyl-tRNA synthetases, PheRS also plays a crucial role in the cellular translation process. Structural characterization demonstrates remarkable architectural diversity ranging from monomer to hetero-oligomer. Heterotetrameric PheRS contains an editing domain to proofread misincorporation of non-cognate amino acids. However, editing activity is absent in monomeric PheRS. PheRS has also shown some noncanonical functions, such as DNA binding properties, suggesting its involvement in complex regulatory pathways. Engineered mutants with relaxed substrate specificities of PheRS can be a promising tool for chemical and synthetic biology. Because of substantial structural variations among species due to evolutionary divergence, PheRS may be validated as a novel drug target. Human PheRS gene mutations have recently been implicated in several neurological disorders prompting structure-function studies to elucidate the molecular role of PheRS in such pathologies. In this review on PheRS, we will briefly cover all of the aforementioned aspects and our current understanding about the enzyme.

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Phenylalanyl-tRNA synthetase from E. coli MRE-600: analysis of the active site distribution on the enzyme subunits by affinity labelling

Cited by 24 publications

References 16 publications

The Role of a Novel Auxiliary Pocket in Bacterial Phenylalanyl-tRNA Synthetase Druggability

The Role of a Novel Auxiliary Pocket in Bacterial Phenylalanyl-tRNA Synthetase Druggability

Structural Aspects of Phenylalanylation and Quality Control in Three Major Forms of Phenylalanyl-tRNA Synthetase

Phenylalanyl-tRNA synthetase

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