Serine---tRNA ligase

 

Serine-tRNA ligase (EC:6.1.1.11) exists as monomer and belongs to the aminoacyl-tRNA synthetase class IIa. It catalyses the attachment of serine to tRNA (Ser). It is also able to aminoacylate tRNA (Sec) with serine, to form the misacylated tRNA L-seryl-tRNA (Sec), which will be further converted into selenocysteinyl-tRNA (Sec).

 

Reference Protein and Structure

Sequence
P34945 UniProt (6.1.1.11) IPR002317 (Sequence Homologues) (PDB Homologues)
Biological species
Thermus thermophilus HB27 (Bacteria) Uniprot
PDB
1ses - CRYSTAL STRUCTURES AT 2.5 ANGSTROMS RESOLUTION OF SERYL-TRNA SYNTHETASE COMPLEXED WITH TWO DIFFERENT ANALOGUES OF SERYL-ADENYLATE (2.5 Å) PDBe PDBsum 1ses
Catalytic CATH Domains
3.30.930.10 CATHdb (see all for 1ses)
Cofactors
Magnesium(2+) (3)
Click To Show Structure

Enzyme Reaction (EC:6.1.1.11)

AMP 3'-end(1-) residue
CHEBI:78442ChEBI
+
L-serine zwitterion
CHEBI:33384ChEBI
+
ATP(4-)
CHEBI:30616ChEBI
→
hydron
CHEBI:15378ChEBI
+
adenosine 5'-monophosphate(2-)
CHEBI:456215ChEBI
+
3'-(L-seryl)adenylyl(1-) group
CHEBI:78533ChEBI
+
diphosphate(3-)
CHEBI:33019ChEBI
Alternative enzyme names: SerRS, Serine translase, Seryl-tRNA synthetase, Seryl-transfer RNA synthetase, Seryl-transfer ribonucleate synthetase, Seryl-transfer ribonucleic acid synthetase,

Enzyme Mechanism

Introduction

This enzyme catalyzes two successive transfer reactions. Firstly, it transfers the adenylate from ATP (the first substrate) to the carboxylate of the second substrate, serine, resulting in the formation of seryl-adenylate (intermediate) and the release of the inorganic pyrophosphate. Secondly, it transfers the acyl group from the intermediate to the 3'-OH of tRNA(Ser). The ATP is found in an unusual bent conformation, stabilised by interactions with conserved arginines and three manganese ions.

Catalytic Residues Roles

UniProt PDB* (1ses)
Glu345, Ser348 Glu345A, Ser348A Forms the metal binding site. metal ligand
Arg386, Arg256, Arg271 Arg386A, Arg256A, Arg271A Stabilises the negatively charged groups, the acceptor group (the carboxylate) and the transferred group (apha-phosphate of ATP), by neutralising the charged groups. electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Belrhali H et al. (1995), Structure, 3, 341-352. The structural basis for seryl-adenylate and Ap4A synthesis by seryl-tRNA synthetase. PMID:7613865.
  2. Cusack S et al. (1996), EMBO J, 15, 2834-2842. The crystal structure of the ternary complex of T.thermophilus seryl-tRNA synthetase with tRNA(Ser) and a seryl-adenylate analogue reveals a conformational switch in the active site. PMID:8654381.
  3. Belrhali H et al. (1994), Science, 263, 1432-1436. Crystal structures at 2.5 angstrom resolution of seryl-tRNA synthetase complexed with two analogs of seryl adenylate. PMID:8128224.
  4. Fujinaga M et al. (1993), J Mol Biol, 234, 222-233. Refined crystal structure of the seryl-tRNA synthetase from Thermus thermophilus at 2.5 A resolution. DOI:10.1006/jmbi.1993.1576. PMID:8230201.

Step 1.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Glu345A metal ligand
Ser348A metal ligand
Arg256A electrostatic stabiliser
Arg271A electrostatic stabiliser
Arg386A electrostatic stabiliser

Chemical Components

Step 1.

Contributors

Christian Drew, Craig Porter, Gemma L. Holliday