Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

thrS (P0A8M3) - Overview - Molecular Target Synopsis

Protein


thrS, Threonine--tRNA ligase
Enzyme Classification 6.1.1.3
UniProt P0A8M3

Also Known as SYT_ECOLI, thrS

Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: L-threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr) (PubMed:15079065, PubMed:10881191, PubMed:18997014). The rate-limiting step is amino acid activation in the presence of tRNA (PubMed:18997014). The 2'-OH of the acceptor base (adenine 76, A76) of tRNA(Thr) and His-309 collaborate to transfer L-Thr to the tRNA; substitution of 2'-OH of A76 with hydrogen or fluorine decreases transfer efficiency 760 and 100-fold respectively (PubMed:18997014). The zinc ion in the active site discriminates against charging of the isosteric amino acid valine (PubMed:10881191). Also activates L-serine, but does not detectably transfer it to tRNA(Thr) (PubMed:15079065). Edits incorrectly charged L-seryl-tRNA(Thr) via its editing domain (PubMed:15079065, PubMed:11136973, PubMed:15525511), in a post-transfer reaction probably via water-mediated hydrolysis (PubMed:15525511)., ThrS is also a translational repressor protein, it controls binds its own mRNA in the operator region upstream of the start codon (PubMed:3086882). The mRNA region upstream of the start codon has a tRNA-like secondary structure; mRNA and tRNA compete for binding to ThrRS (PubMed:2254931). ThrRS represses translation by preventing the ribosome from to mRNA, and tRNA(Thr) acts as an antirepressor allowing fine level control of enzyme synthesis (PubMed:2254931). X-ray structures prove that operator mRNA and tRNA bind to overlapping sites in the protein (PubMed:10319817, PubMed:11953757). Homodimer (PubMed:10319817, PubMed:11136973, PubMed:10881191, PubMed:11953757, PubMed:23362938, PubMed:25824639); binds 2 tRNA(Thr) per homodimer, each tRNA contacts both monomers and makes specific contacts with the anticodon and acceptor stems (PubMed:10319817).

4P3P
STRUCTURAL BASIS FOR FULL-SPECTRUM INHIBITION OF THREONYL-TRNA SYNTHETASE BY BORRELIDIN 3
RCSB/PDB
Inspect Structure
See all 3D Structures for thrS

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform

Sub-cellular localization


UniProt: thrS is active in the following subcellular-locations: cytoplasm.
GO terms: thrS is active in the following subcellular-locations: cytoplasm, cytosol.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project thrS has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)

3D Structures


For thrS there are:
15 structures (33 chains) solved
14 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

thrS is solved in complex with the approved drug(s):

AMP/ADENOSINE PHOSPHATE (1QF6_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


thrS has been screened with compounds ( bioactivities). (see details)