PDBsum entry 3hxx

Ligase

PDB id: 3hxx

Contents

Protein chain

441 a.a. *

Ligands

ACP

Metals

_MG ×3

Waters ×377

* Residue conservation analysis

PDB id:

3hxx

Name:

Ligase

Title:

Crystal structure of catalytic fragment of e. Coli alars in complex with amppcp

Structure:

Alanyl-tRNA synthetase. Chain: a. Fragment: n-terminal catalytic fragment residues 2-442. Synonym: alanine-tRNA ligase, alars. Engineered: yes. Mutation: yes

Source:

Escherichia coli. Organism_taxid: 83333. Strain: k-12. Gene: alas, lovb, b2697, jw2667. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.11Å R-factor: 0.179 R-free: 0.234

Authors:

M.Guo,X.-L.Yang,P.Schimmel

Key ref:

M.Guo et al. (2009). Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma. Nature, 462, 808-812. PubMed id: 20010690

Date:

22-Jun-09 Release date: 15-Dec-09

Protein chain

P00957  (SYA_ECOLI) -  Alanine--tRNA ligase from Escherichia coli (strain K12)

Seq: 876 a.a.

Struc: 441 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.6.1.1.7 - alanine--tRNA ligase.
• Reaction: tRNA(Ala) + L-alanine + ATP = L-alanyl-tRNA(Ala) + AMP + diphosphate

tRNA(Ala) + L-alanine + ATP = L-alanyl-tRNA(Ala) (Bound ligand (Het Group name = ACP) matches with 74.19% similarity) + AMP + diphosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Nature 462:808-812 (2009)

PubMed id: 20010690

Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma.

M.Guo, Y.E.Chong, R.Shapiro, K.Beebe, X.L.Yang, P.Schimmel.

ABSTRACT

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.