Structure of Pyrrolysyl-tRNA Synthetase, an Archaeal Enzyme for Genetic Code Innovation

Journal Article · Mon Jan 01 04:00:00 EST 2007 · Proceedings of the National Academy of Sciences of the USA

DOI:https://doi.org/10.1073/pnas.0704769104· OSTI ID:959485

Kavran, J; Gundllapalli, S; O'Donoghue, P; Englert, M; Soll, D; Steitz, T

Pyrrolysine (Pyl), the 22nd natural amino acid and genetically encoded by UAG, becomes attached to its cognate tRNA by pyrrolysyl-tRNA synthetase (PylRS). We have determined three crystal structures of the Methanosarcina mazei PylRS complexed with either AMP-PNP, Pyl-AMP plus pyrophosphate, or the Pyl analogue N-e-[(cylopentyloxy)carbonyl]-l-lysine plus ATP. The structures reveal that PylRS utilizes a deep hydrophobic pocket for recognition of the Pyl side chain. A comparison of these structures with previously determined class II tRNA synthetase complexes illustrates that different substrate specificities derive from changes in a small number of residues that form the substrate side-chain-binding pocket. The knowledge of these structures allowed the placement of PylRS in the aminoacyl-tRNA synthetase (aaRS) tree as the last known synthetase that evolved for genetic code expansion, as well as the finding that Pyl arose before the last universal common ancestral state. The PylRS structure provides an excellent framework for designing new aaRSs with altered amino acid specificity.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 959485
• Report Number(s): BNL--82471-2009-JA
• Journal Information: Proceedings of the National Academy of Sciences of the USA, Journal Name: Proceedings of the National Academy of Sciences of the USA Journal Issue: 27 Vol. 104; ISSN 0027-8424; ISSN PNASA6
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
AMINO ACIDS
CRYSTAL STRUCTURE
ENZYMES
GENETICS
LIGASES
RESIDUES
SPECIFICITY
SUBSTRATES
TREES
national synchrotron light source