PDBsum entry 5thh

Ligase

PDB id: 5thh

Contents

Protein chain

329 a.a.

Ligands

TYR

Waters ×288

PDB id:

5thh

Name:

Ligase

Title:

Crystal structure of a human tyrosyl-tRNA synthetase mutant

Structure:

Tyrosine--tRNA ligase, cytoplasmic. Chain: a. Synonym: tyrosyl-tRNA synthetase,tyrrs. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: yars. Expressed in: escherichia coli 'bl21-gold(de3)plyss ag'. Expression_system_taxid: 866768

Resolution:

1.96Å R-factor: 0.180 R-free: 0.219

Authors:

D.Blocquel,X.L.Yang

Key ref:

D.Blocquel et al. (2017). Alternative stable conformation capable of protein misinteraction links tRNA synthetase to peripheral neuropathy. Nucleic Acids Res, 45, 8091-8104. PubMed id: 28531329

Date:

29-Sep-16 Release date: 17-May-17

Protein chain

P54577  (SYYC_HUMAN) -  Tyrosine--tRNA ligase, cytoplasmic from Homo sapiens

Seq: 528 a.a.

Struc: 329 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.6.1.1.1 - tyrosine--tRNA ligase.
• Reaction: tRNA(Tyr) + L-tyrosine + ATP = L-tyrosyl-tRNA(Tyr) + AMP + diphosphate + H⁺

tRNA(Tyr) + L-tyrosine (Bound ligand (Het Group name = TYR) corresponds exactly) + ATP = L-tyrosyl-tRNA(Tyr) + AMP + diphosphate + H(+)

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

reference

Nucleic Acids Res 45:8091-8104 (2017)

PubMed id: 28531329

Alternative stable conformation capable of protein misinteraction links tRNA synthetase to peripheral neuropathy.

D.Blocquel, S.Li, N.Wei, H.Daub, M.Sajish, M.L.Erfurth, G.Kooi, J.Zhou, G.Bai, P.Schimmel, A.Jordanova, X.L.Yang.

ABSTRACT

While having multiple aminoacyl-tRNA synthetases implicated in Charcot-Marie-Tooth (CMT) disease suggests a common mechanism, a defect in enzymatic activity is not shared among the CMT-causing mutants. Protein misfolding is a common hypothesis underlying the development of many neurological diseases. Its process usually involves an initial reduction in protein stability and then the subsequent oligomerization and aggregation. Here, we study the structural effect of three CMT-causing mutations in tyrosyl-tRNA synthetase (TyrRS or YARS). Through various approaches, we found that the mutations do not induce changes in protein secondary structures, or shared effects on oligomerization state and stability. However, all mutations provide access to a surface masked in the wild-type enzyme, and that access correlates with protein misinteraction. With recent data on another CMT-linked tRNA synthetase, we suggest that an inherent plasticity, engendering the formation of alternative stable conformations capable of aberrant interactions, links the tRNA synthetase family to CMT.