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
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Research Support, N.I.H., Extramural
MeSH terms
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Biocatalysis
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Catalytic Domain
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Crystallography, X-Ray
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Cyclization
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Dipeptides / biosynthesis*
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Esterification
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Glutamic Acid / chemistry
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Glutamic Acid / metabolism
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Models, Molecular
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Mycobacterium tuberculosis / enzymology*
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Peptide Synthases / chemistry*
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Peptide Synthases / metabolism*
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Peptides, Cyclic / biosynthesis*
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Protein Conformation
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RNA, Transfer, Tyr / chemistry
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RNA, Transfer, Tyr / metabolism
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Serine / genetics
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Serine / metabolism
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Tyrosine / chemistry
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Tyrosine / metabolism
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Tyrosine-tRNA Ligase / chemistry*
Substances
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Dipeptides
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Peptides, Cyclic
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RNA, Transfer, Tyr
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Glutamic Acid
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Tyrosine
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Serine
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Tyrosine-tRNA Ligase
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Peptide Synthases
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cyclopeptide synthetase