Human Prolyl-tRNA Synthetase in Complex with L-proline and Compound 4h

Towards Novel 3-Aminopyrazinamide-Based Prolyl-tRNA Synthetase Inhibitors: In Silico Modelling, Thermal Shift Assay and Structural Studies.

Bifunctional glutamate/proline--tRNA ligase

Bifunctional aminoacyl-tRNA synthetase,Cell proliferation-inducing gene 32 protein,Glutamatyl-prolyl-tRNA synthetase

GAGEGQGPKKQTRLGLEAKKEENLADWYSQVITKSEMIEYHDISGCYILRPWAYAIWEAIKDFFDAEIKKLGVENCYFPM
FVSQSALEKEKTHVADFAPEVAWVTRSGKTELAEPIAIRPTSETVMYPAYAKWVQSHRDLPIKLNQWCNVVRWEFKHPQP
FLRTREFLWQEGHSAFATMEEAAEEVLQILDLYAQVYEELLAIPVVKGRKTEKEKFAGGDYTTTIEAFISASGRAIQGGT
SHHLGQNFSKMFEIVFEDPKIPGEKQFAYQNSWGLTTRTIGVMTMVHGDNMGLVLPPRVACVQVVIIPCGITNALSEEDK
EALIAKCNDYRRRLLSVNIRVRADLRDNYSPGWKFNHWELKGVPIRLEVGPRDMKSCQFVAVRRDTGEKLTVAENEAETK
LQAILEDIQVTLFTRASEDLKTHMVVANTMEDFQKILDSGKIVQIPFCGEIDCEDWIKKTTARDQDLEPGAPSMGAKSLC
IPFKPLCELQPGAKCVCGKNPAKYYTLFGRSY

EPRS1, EPRS, GLNS, PARS, QARS, QPRS, PIG32

The purified protein at 30 mg/mL in 10 mM Tris pH 7, 100 mM NaCl, 2.5 mM 2-mercaptoethanol was incubated with 10 mM L-proline, 2 mM compound and 12% (v/v) DMSO on ice for 1 hr. Crystals were grown in a Terasaki Microbatch plate by mixing 1 uL the pre-mix with 1 uL of reservoir solution containing 0.25-0.4 M SrCl2, 15-20% (v/v) PEG3350 and 100 mM HEPES pH 7.5. The drops were covered with paraffin oil. Crystals were flash frozen in liquid nitrogen directly from the plate.

chain 'A' and (resid 1015 through 1287 )

chain 'A' and (resid 1288 through 1512 )

chain 'B' and (resid 1015 through 1151 )

chain 'B' and (resid 1152 through 1296 )

chain 'B' and (resid 1297 through 1512 )

beta barrel, tRNA synthetase, protein-inhibitor complex, LIGASE