1LI7

Crystal Structure of Cysteinyl-tRNA Synthetase with Cysteine Substrate Bound

Summary for 1LI7

• Entry DOI: 10.2210/pdb1li7/pdb
• Related: 1LI5
• Descriptor: CYSTEINYL-TRNA SYNTHETASE, ZINC ION, CYSTEINE, ... (4 entities in total)
• Functional Keywords: trna synthetase, cysteine, e.coli, ligase
• Biological source: Escherichia coli
• Cellular location: Cytoplasm: P21888
• Total number of polymer chains: 2
• Total formula weight: 104915.25

Authors

Newberry, K.J.,Hou, Y.-M.,Perona, J.J. (deposition date: 2002-04-17, release date: 2002-04-26, Last modification date: 2023-08-16)

Primary citation

Newberry, K.J.,Hou, Y.-M.,Perona, J.J.
Structural origins of amino acid selection without editing by cysteinyl-tRNA synthetase
EMBO J., 21:2778-2787, 2002

PubMed Abstract: Cysteinyl-tRNA synthetase (CysRS) is highly specific for synthesis of cysteinyl adenylate, yet does not possess the amino acid editing activity characteristic of many other tRNA synthetases. To elucidate how CysRS is able to distinguish cysteine from non-cognate amino acids, crystal structures of the Escherichia coli enzyme were determined in apo and cysteine-bound states. The structures reveal that the substrate cysteine thiolate forms a single direct interaction with a zinc ion bound at the base of the active site cleft, in a trigonal bipyramidal geometry together with four highly conserved protein side chains. Cysteine binding induces movement of the zinc ion towards substrate, as well as flipping of the conserved Trp205 indole ring to pack on the thiol side chain. The imidazole groups of five conserved histidines lie adjacent to the zinc ion, forming a unique arrangement suggestive of functional significance. Thus, amino acid discrimination without editing arises most directly from the favorable zinc-thiolate interaction, which is not possible for non-cognate substrates. Additional selectivity may be generated during the induced-fit conformational changes that help assemble the active site.

PubMed: 12032090
DOI: 10.1093/emboj/21.11.2778

Experimental method

X-RAY DIFFRACTION (2.6 Å)