Transcript Valyl tRNA-Synthestase - Illinois State University

Overall Structure
Editing Domain
(“2nd Sieve”)
862 amino acids
25 α-helices
30 β-strands
Catalytic Domain
(“1st Sieve”)
C-Terminal
Coiled-Coil
Domain
Anticodon
Binding Domain
Function
• Aminoacyl tRNA
synthetases are
enzymes that
catalyze the
esterification of a
specific amino acid
to a compatible
cognate tRNA to
form an aminoacyltRNA
• Class I vs. Class II:
– 2’-OH, then 3’-OH
– Directly to 3’-OH
“Double-Sieve” Concept
Aminoacylation Site Interactions
Hydrophobic Pocket
Trp456
Trp491
Asp81
Pro42
Pro41
Ile491
Asn44
KMSKS Loop
Met529
Editing Domain Interactions
Leu269
Glu281
Glu261
Phe264
Thr214
Tyr337
Leu278
Editing Hydrophilic Pocket
Anticodon Binding Domain
*nucleotides are in green,
amino acids are in yellow
Kinetics for C-term. Domain
o phosphates on A20 & A21
interact through salt bridges with
Arg818 and Arg843
o G19 & C56 crucial of correct
positioning of 3’ CCA end of
tRNA into aminoacylation
catalytic site
References
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Fukai, S.; Nureki, O.; Sekine, S.; Shimada, A.; Tao, J.; Vassylyev, D.G.; Yokoyama, S.
Structural Basis for Double-Sieve Discrimination of L-Valine from L-Isoleucine and LThreonine by the Complex of tRNAVal and Valyl-tRNA Synthetase. Cell 2000, 103, 793-803.
Fukai, S.; Nureki, O.; Sekine, S.; Shimada, A.; Vassylyev, D.G.; Yogoyama, S. Mechanism of
molecular interactions for tRNAVal recognition by valyl-tRNA synthetase. RNA 2003, 9, 100111.
Fukunaga, R.; Yokoyama, S. Structural Basis for Non-cognate Amino Acid Discrimination
by the Valyl-tRNA Synthetase Editing Domain. J. Bio. Chem. 2005, 280 (33), 29937-29945.
Liu, M.; Chu, W.; Liu, J.C.H.; Horowitz, J. Role of acceptor stem conformation in tRNAVal
recognition by its cognate synthetase. Nucleic Acids Res. 1997, 25, 4883-4890.