3IAL

Giardia lamblia Prolyl-tRNA synthetase in complex with prolyl-adenylate

Summary for 3IAL

• Entry DOI: 10.2210/pdb3ial/pdb
• Descriptor: Prolyl-tRNA synthetase, 5'-O-[(R)-hydroxy{[(2S)-pyrrolidin-2-ylcarbonyl]oxy}phosphoryl]adenosine, GLYCEROL, ... (4 entities in total)
• Functional Keywords: aminoacyl-trna synthetase, trna ligase, aars, prors, cysrs, pro(cys)rs, translation, atp-binding, nucleotide-binding, structural genomics, medical structural genomics of pathogenic protazoa, msgpp, ligase, medical structural genomics of pathogenic protozoa
• Biological source: Giardia lamblia ATCC 50803
• Total number of polymer chains: 2
• Total formula weight: 118461.22

Authors

Larson, E.T.,Merritt, E.A.,Medical Structural Genomics of Pathogenic Protozoa,Medical Structural Genomics of Pathogenic Protozoa (MSGPP) (deposition date: 2009-07-14, release date: 2009-08-11, Last modification date: 2023-09-06)

Primary citation

Larson, E.T.,Kim, J.E.,Napuli, A.J.,Verlinde, C.L.,Fan, E.,Zucker, F.H.,Van Voorhis, W.C.,Buckner, F.S.,Hol, W.G.,Merritt, E.A.
Structure of the prolyl-tRNA synthetase from the eukaryotic pathogen Giardia lamblia.
Acta Crystallogr.,Sect.D, 68:1194-1200, 2012

PubMed Abstract: The genome of the human intestinal parasite Giardia lamblia contains only a single aminoacyl-tRNA synthetase gene for each amino acid. The Giardia prolyl-tRNA synthetase gene product was originally misidentified as a dual-specificity Pro/Cys enzyme, in part owing to its unexpectedly high off-target activation of cysteine, but is now believed to be a normal representative of the class of archaeal/eukaryotic prolyl-tRNA synthetases. The 2.2 Å resolution crystal structure of the G. lamblia enzyme presented here is thus the first structure determination of a prolyl-tRNA synthetase from a eukaryote. The relative occupancies of substrate (proline) and product (prolyl-AMP) in the active site are consistent with half-of-the-sites reactivity, as is the observed biphasic thermal denaturation curve for the protein in the presence of proline and MgATP. However, no corresponding induced asymmetry is evident in the structure of the protein. No thermal stabilization is observed in the presence of cysteine and ATP. The implied low affinity for the off-target activation product cysteinyl-AMP suggests that translational fidelity in Giardia is aided by the rapid release of misactivated cysteine.

PubMed: 22948920
DOI: 10.1107/S0907444912024699

Experimental method

X-RAY DIFFRACTION (2.2 Å)