The structure and mechanism of the Mycobacterium tuberculosis cyclodityrosine synthetase

Nat Chem Biol. 2010 Nov;6(11):797-9. doi: 10.1038/nchembio.440. Epub 2010 Sep 19.

Abstract

The Mycobacterium tuberculosis enzyme Rv2275 catalyzes the formation of cyclo(L-Tyr-L-Tyr) using two molecules of Tyr-tRNA(Tyr) as substrates. The three-dimensional (3D) structure of Rv2275 was determined to 2.0-Å resolution, revealing that Rv2275 is structurally related to the class Ic aminoacyl-tRNA synthetase family of enzymes. Mutagenesis and radioactive labeling suggests a covalent intermediate in which L-tyrosine is transferred from Tyr-tRNA(Tyr) to an active site serine (Ser88) by transesterification with Glu233 serving as a critical base, catalyzing dipeptide bond formation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biocatalysis
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cyclization
  • Dipeptides / biosynthesis*
  • Esterification
  • Glutamic Acid / chemistry
  • Glutamic Acid / metabolism
  • Models, Molecular
  • Mycobacterium tuberculosis / enzymology*
  • Peptide Synthases / chemistry*
  • Peptide Synthases / metabolism*
  • Peptides, Cyclic / biosynthesis*
  • Protein Conformation
  • RNA, Transfer, Tyr / chemistry
  • RNA, Transfer, Tyr / metabolism
  • Serine / genetics
  • Serine / metabolism
  • Tyrosine / chemistry
  • Tyrosine / metabolism
  • Tyrosine-tRNA Ligase / chemistry*

Substances

  • Dipeptides
  • Peptides, Cyclic
  • RNA, Transfer, Tyr
  • Glutamic Acid
  • Tyrosine
  • Serine
  • Tyrosine-tRNA Ligase
  • Peptide Synthases
  • cyclopeptide synthetase

Associated data

  • PDB/2X9Q