Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy

Xie S, Metcalfe R, Dunn E, Morton C, Huang S, Puhalovich T, Du Y, Wittlin S, Nie S, Luth M, Ma L, Kim M, Pasaje C, Kumpornsin K, Giannangelo C, Houghton F, Churchyard A, Famodimu M, Barry D, Gillett D, Dey S, Kosasih C, Newman W, Niles J, Lee M, Baum J, Ottilie S, Winzeler E, Creek D, Williamson N, Parker M, Brand S, Langston S, Dick L, Griffin M, Gould A, Tilley L, Science 376(6597):1074-1079 (2022) DOI

SASDME4 – Human tyrosyl tRNA synthetase

Tyrosine--tRNA ligase, cytoplasmic
MWexperimental 75 kDa
MWexpected 82 kDa
VPorod 118 nm3
log I(s) 2.04×10-2 2.04×10-3 2.04×10-4 2.04×10-5
Tyrosine--tRNA ligase, cytoplasmic small angle scattering data  s, nm-1
ln I(s)
Tyrosine--tRNA ligase, cytoplasmic Guinier plot ln 2.04×10-2 Rg: 3.6 nm 0 (3.6 nm)-2 s2
(sRg)2I(s)/I(0)
Tyrosine--tRNA ligase, cytoplasmic Kratky plot 1.104 0 √3 sRg
p(r)
Tyrosine--tRNA ligase, cytoplasmic pair distance distribution function Rg: 3.7 nm 0 Dmax: 11.5 nm

Data validation

Fits and models

log I(s)
 s, nm-1
Tyrosine--tRNA ligase, cytoplasmic OTHER model
Synchrotron SAXS data from solutions of Human tyrosyl tRNA synthetase in 20 mM Tris-HCl, 150 mM NaCl, 0.5 mM TCEP, 0.1% sodium azide, pH 7.4 were collected on the SAXS/WAXS beam line at the Australian Synchrotron (Melbourne, Australia) using a Pilatus3 S 2M detector at a sample-detector distance of 2.2 m and at a wavelength of λ = 0.1078 nm (I(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). In-line size-exclusion chromatography co-flow SEC-SAXS was employed. The SEC parameters were as follows: A sample was injected at a 0.40 ml/min flow rate onto a GE Superdex 200 Increase 5/150 column at 20°C. 14 successive 1 second frames were collected. The data were normalized to the intensity of the transmitted beam and radially averaged; the scattering of the solvent-blank was subtracted.

Sample injection volume = UNKNOWN

Tyrosine--tRNA ligase, cytoplasmic (HsYRS)
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Dimer
Mon. MW   41.1 kDa
 
UniProt   P54577 (1-364)
Sequence   FASTA
 
PDB ID   7ROU