The structure and mechanism of the Mycobacterium tuberculosis cyclodityrosine synthetase

Matthew W. Vetting; Subray S. Hegde; John S. Blanchard

doi:10.1038/nchembio.440

The structure and mechanism of the Mycobacterium tuberculosis cyclodityrosine synthetase

Matthew W. Vetting, Subray S. Hegde, John S. Blanchard

Research output: Contribution to journal › Article › peer-review

58 Scopus citations

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.

Original language	English (US)
Pages (from-to)	797-799
Number of pages	3
Journal	Nature Chemical Biology
Volume	6
Issue number	11
DOIs	https://doi.org/10.1038/nchembio.440
State	Published - Nov 2010
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nchembio.440

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title = "The structure and mechanism of the Mycobacterium tuberculosis cyclodityrosine synthetase",

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-{\AA} 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.",

author = "Vetting, {Matthew W.} and Hegde, {Subray S.} and Blanchard, {John S.}",

note = "Funding Information: We thank S. Del Amo and M. Callaway (Albert Einstein College of Medicine) for their help in cYY synthesis and ESI mass spectrometry, respectively. This work was supported by US National Institutes of Health Grant A133696.",

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AU - Hegde, Subray S.

AU - Blanchard, John S.

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The structure and mechanism of the Mycobacterium tuberculosis cyclodityrosine synthetase

Abstract

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