ß-Lysine discrimination by lysyl-tRNA synthetase

Marla S Gilreath; Hervé Roy; Tammy J Bullwinkle; Assaf Katz; William W Navarre; Michael Ibba

doi:10.1016/j.febslet.2011.09.008

ß-Lysine discrimination by lysyl-tRNA synthetase

Marla S Gilreath, Hervé Roy, Tammy J Bullwinkle, Assaf Katz, William W Navarre, Michael Ibba

Transcription, RNA, and Gene Medicine Program

12 Citations (Scopus)

Abstract

Elongation factor P is modified with (R)-β-lysine by the lysyl-tRNA synthetase (LysRS) paralog PoxA. PoxA specificity is orthogonal to LysRS, despite their high similarity. To investigate α- and β-lysine recognition by LysRS and PoxA, amino acid replacements were made in the LysRS active site guided by the PoxA structure. A233S LysRS behaved as wild type with α-lysine, while the G469A and A233S/G469A variants decreased stable α-lysyl-adenylate formation. A233S LysRS recognized β-lysine better than wildtype, suggesting a role for this residue in discriminating α- and β-amino acids. Both enantiomers of β-lysine were substrates for tRNA aminoacylation by LysRS, which, together with the relaxed specificity of the A233S variant, suggest a possible means to develop systems for in vivo co-translational insertion of β-amino acids.

Original language	English
Journal	F E B S Letters
Volume	585
Issue number	20
Pages (from-to)	3284-8
Number of pages	5
ISSN	0014-5793
DOIs	https://doi.org/10.1016/j.febslet.2011.09.008
Publication status	Published - 20 Oct 2011

Keywords

Amino Acid Substitution
Bacillus cereus
Bacterial Proteins
Lysine
Lysine-tRNA Ligase
Mutation, Missense
Peptide Elongation Factors

Access to Document

10.1016/j.febslet.2011.09.008

Cite this

Gilreath, M. S., Roy, H., Bullwinkle, T. J., Katz, A., Navarre, W. W., & Ibba, M. (2011). ß-Lysine discrimination by lysyl-tRNA synthetase. F E B S Letters, 585(20), 3284-8. https://doi.org/10.1016/j.febslet.2011.09.008

@article{434b8f7cfd094d47839da2c61390fbef,

title = "{\ss}-Lysine discrimination by lysyl-tRNA synthetase",

abstract = "Elongation factor P is modified with (R)-β-lysine by the lysyl-tRNA synthetase (LysRS) paralog PoxA. PoxA specificity is orthogonal to LysRS, despite their high similarity. To investigate α- and β-lysine recognition by LysRS and PoxA, amino acid replacements were made in the LysRS active site guided by the PoxA structure. A233S LysRS behaved as wild type with α-lysine, while the G469A and A233S/G469A variants decreased stable α-lysyl-adenylate formation. A233S LysRS recognized β-lysine better than wildtype, suggesting a role for this residue in discriminating α- and β-amino acids. Both enantiomers of β-lysine were substrates for tRNA aminoacylation by LysRS, which, together with the relaxed specificity of the A233S variant, suggest a possible means to develop systems for in vivo co-translational insertion of β-amino acids.",

keywords = "Amino Acid Substitution, Bacillus cereus, Bacterial Proteins, Lysine, Lysine-tRNA Ligase, Mutation, Missense, Peptide Elongation Factors",

author = "Gilreath, {Marla S} and Herv{\'e} Roy and Bullwinkle, {Tammy J} and Assaf Katz and Navarre, {William W} and Michael Ibba",

year = "2011",

month = oct,

day = "20",

doi = "10.1016/j.febslet.2011.09.008",

language = "English",

volume = "585",

pages = "3284--8",

journal = "F E B S Letters",

issn = "0014-5793",

publisher = "JohnWiley & Sons Ltd",

number = "20",

}

TY - JOUR

T1 - ß-Lysine discrimination by lysyl-tRNA synthetase

AU - Gilreath, Marla S

AU - Roy, Hervé

AU - Bullwinkle, Tammy J

AU - Katz, Assaf

AU - Navarre, William W

AU - Ibba, Michael

PY - 2011/10/20

Y1 - 2011/10/20

N2 - Elongation factor P is modified with (R)-β-lysine by the lysyl-tRNA synthetase (LysRS) paralog PoxA. PoxA specificity is orthogonal to LysRS, despite their high similarity. To investigate α- and β-lysine recognition by LysRS and PoxA, amino acid replacements were made in the LysRS active site guided by the PoxA structure. A233S LysRS behaved as wild type with α-lysine, while the G469A and A233S/G469A variants decreased stable α-lysyl-adenylate formation. A233S LysRS recognized β-lysine better than wildtype, suggesting a role for this residue in discriminating α- and β-amino acids. Both enantiomers of β-lysine were substrates for tRNA aminoacylation by LysRS, which, together with the relaxed specificity of the A233S variant, suggest a possible means to develop systems for in vivo co-translational insertion of β-amino acids.

AB - Elongation factor P is modified with (R)-β-lysine by the lysyl-tRNA synthetase (LysRS) paralog PoxA. PoxA specificity is orthogonal to LysRS, despite their high similarity. To investigate α- and β-lysine recognition by LysRS and PoxA, amino acid replacements were made in the LysRS active site guided by the PoxA structure. A233S LysRS behaved as wild type with α-lysine, while the G469A and A233S/G469A variants decreased stable α-lysyl-adenylate formation. A233S LysRS recognized β-lysine better than wildtype, suggesting a role for this residue in discriminating α- and β-amino acids. Both enantiomers of β-lysine were substrates for tRNA aminoacylation by LysRS, which, together with the relaxed specificity of the A233S variant, suggest a possible means to develop systems for in vivo co-translational insertion of β-amino acids.

KW - Amino Acid Substitution

KW - Bacillus cereus

KW - Bacterial Proteins

KW - Lysine

KW - Lysine-tRNA Ligase

KW - Mutation, Missense

KW - Peptide Elongation Factors

U2 - 10.1016/j.febslet.2011.09.008

DO - 10.1016/j.febslet.2011.09.008

M3 - Journal article

C2 - 21925499

SN - 0014-5793

VL - 585

SP - 3284

EP - 3288

JO - F E B S Letters

JF - F E B S Letters

IS - 20

ER -

ß-Lysine discrimination by lysyl-tRNA synthetase

Abstract

Keywords

Access to Document

Fingerprint

Cite this