Jun 25, 1996

The synthetic/editing active site of an aminoacyl-tRNA synthetase: evidence for binding of thiols in the editing subsite

Biochemistry
H Jakubowski

Abstract

The active site of methionyl-tRNA synthetase (MetRS) possesses two functions: synthetic, which provides Met-tRNA for protein synthesis, and editing, which rejects inadvertently misactivated homocysteine. During editing, the side chain -SH group of homocysteine reacts with its activated carboxyl group forming a cyclic thioester, homocysteine thiolactone. As shown here, the side chain -SH and the activated carboxyl groups do not need to be present on the same molecule for the editing to occur. Thioester formation occurs when a thiol and activated methionine, in the form of Met-tRNA, are incubated with MetRS. Depending on the structure of thiols, methionine thioesters may undergo secondary acyl transfer reactions to cis amino, hydroxy, or carboxyl groups which yield methionine dipeptides, esters, or anhydrides, respectively. At saturating thiol concentrations, formation of some thiol derivatives of methionine is as fast as formation of homocysteine thiolactone. Thiol specificity of the reaction and noncompetitive inhibition by the cognate methionine, as well as structure-function studies of active site MetRS mutants, all indicate that there is a specific -SH binding subsite, distinct from the methionine binding subsite, in the syn...Continue Reading

  • References
  • Citations10

References

  • We're still populating references for this paper, please check back later.

Mentioned in this Paper

Thioester Biosynthetic Process
MARS
Derivatives
Alkalescens-Dispar Group
Anhydrides
Noncompetitive Inhibition
Thioester
MT-TA gene
Proteins, Recombinant DNA
Triplet Codon-amino Acid Adaptor Activity

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Bone Marrow Neoplasms

Bone Marrow Neoplasms are cancers that occur in the bone marrow. Discover the latest research on Bone Marrow Neoplasms here.

IGA Glomerulonephritis

IgA glomerulonephritis is a chronic form of glomerulonephritis characterized by deposits of predominantly Iimmunoglobin A in the mesangial area. Discover the latest research on IgA glomerulonephritis here.

Cryogenic Electron Microscopy

Cryogenic electron microscopy (Cryo-EM) allows the determination of biological macromolecules and their assemblies at a near-atomic resolution. Here is the latest research.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

LRRK2 & Immunity During Infection

Mutations in the LRRK2 gene are a risk-factor for developing Parkinson’s disease. However, LRRK2 has been shown to function as a central regulator of vesicular trafficking, infection, immunity, and inflammation. Here is the latest research on the role of this kinase on immunity during infection.

Antiphospholipid Syndrome

Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by the presence of antibodies directed against phospholipids.

Meningococcal Myelitis

Meningococcal myelitis is characterized by inflammation and myelin damage to the meninges and spinal cord. Discover the latest research on meningococcal myelitis here.

Alzheimer's Disease: MS4A

Variants within membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease by recent genome-wide association studies. Here is the latest research.