3hy1

Crystal Structure of catalytic fragment of E. coli AlaRS G237A in complex with SerSA

spinqualitylabelsall models 3hy1, resolution 2.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3hy1 is a 2 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: HED, MES, MG, SO4, SSA Related: 3hxu, 3hxv, 3hxw, 3hxx, 3hxy, 3hxz, 3hy0 Gene: alaS, lovB, b2697, JW2667 (ECOLI) Activity: Alanine--tRNA ligase, with EC number 6.1.1.7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [SYA_ECOLI] Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). AlaRS also incorrectly activates the sterically smaller than alanine amino acid glycine as well as the sterically larger amino acid serine. These incorrectly charged amino acids occur because the of inherent physicochemical limitations on discrimination between closely related amino acids (glycine and serine) in the charging step. Edits incorrectly charged Ser-tRNA(Ala) and Gly-tRNA(Ala) but not incorrectly charged Ser-tRNA(Thr). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Mistranslation arising from confusion of serine for alanine by alanyl-tRNA synthetases (AlaRSs) has profound functional consequences. Throughout evolution, two editing checkpoints prevent disease-causing mistranslation from confusing glycine or serine for alanine at the active site of AlaRS. In both bacteria and mice, Ser poses a bigger challenge than Gly. One checkpoint is the AlaRS editing centre, and the other is from widely distributed AlaXps-free-standing, genome-encoded editing proteins that clear Ser-tRNA(Ala). The paradox of misincorporating both a smaller (glycine) and a larger (serine) amino acid suggests a deep conflict for nature-designed AlaRS. Here we show the chemical basis for this conflict. Nine crystal structures, together with kinetic and mutational analysis, provided snapshots of adenylate formation for each amino acid. An inherent dilemma is posed by constraints of a structural design that pins down the alpha-amino group of the bound amino acid by using an acidic residue. This design, dating back more than 3 billion years, creates a serendipitous interaction with the serine OH that is difficult to avoid. Apparently because no better architecture for the recognition of alanine could be found, the serine misactivation problem was solved through free-standing AlaXps, which appeared contemporaneously with early AlaRSs. The results reveal unconventional problems and solutions arising from the historical design of the protein synthesis machinery. Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma.,Guo M, Chong YE, Shapiro R, Beebe K, Yang XL, Schimmel P Nature. 2009 Dec 10;462(7274):808-12. PMID:20010690 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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