4R1J

Crystal structure of Arc1p-C

Summary for 4R1J

• Entry DOI: 10.2210/pdb4r1j/pdb
• Descriptor: GU4 nucleic-binding protein 1, GLYCEROL (3 entities in total)
• Functional Keywords: emap, trna binding, trna, rna binding protein
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Cytoplasm : P46672
• Total number of polymer chains: 1
• Total formula weight: 22147.27

Authors

Altegoer, F.,Bange, G. (deposition date: 2014-08-06, release date: 2015-02-18, Last modification date: 2023-09-20)

Primary citation

Giessen, T.W.,Altegoer, F.,Nebel, A.J.,Steinbach, R.M.,Bange, G.,Marahiel, M.A.
A Synthetic Adenylation-Domain-Based tRNA-Aminoacylation Catalyst.
Angew.Chem.Int.Ed.Engl., 54:2492-2496, 2015

PubMed Abstract: The incorporation of non-proteinogenic amino acids represents a major challenge for the creation of functionalized proteins. The ribosomal pathway is limited to the 20-22 proteinogenic amino acids while nonribosomal peptide synthetases (NRPSs) are able to select from hundreds of different monomers. Introduced herein is a fusion-protein-based design for synthetic tRNA-aminoacylation catalysts based on combining NRPS adenylation domains and a small eukaryotic tRNA-binding domain (Arc1p-C). Using rational design, guided by structural insights and molecular modeling, the adenylation domain PheA was fused with Arc1p-C using flexible linkers and achieved tRNA-aminoacylation with both proteinogenic and non-proteinogenic amino acids. The resulting aminoacyl-tRNAs were functionally validated and the catalysts showed broad substrate specificity towards the acceptor tRNA. Our strategy shows how functional tRNA-aminoacylation catalysts can be created for bridging the ribosomal and nonribosomal worlds. This opens up new avenues for the aminoacylation of tRNAs with functional non-proteinogenic amino acids.

PubMed: 25583137
DOI: 10.1002/anie.201410047

Experimental method

X-RAY DIFFRACTION (1.4 Å)