The structure and mechanism of the Mycobacterium tuberculosis cyclodityrosine synthetase.
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.
Vetting
Matthew W
MW
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.
Hegde
Subray S
SS
Blanchard
John S
JS
D055162:Biocatalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003500:Cyclization; D004151:Dipeptides / Q000096:biosynthesis*; D004951:Esterification; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010453:Peptide Synthases / Q000737:chemistry* / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000096:biosynthesis*; D011487:Protein Conformation; D012365:RNA, Transfer, Tyr / Q000737:chemistry / Q000378:metabolism; D012694:Serine / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism; D014448:Tyrosine-tRNA Ligase / Q000737:chemistry*
D004151:Dipeptides; D010456:Peptides, Cyclic; D012365:RNA, Transfer, Tyr; D018698:Glutamic Acid; D014443:Tyrosine; D012694:Serine; D014448:Tyrosine-tRNA Ligase; D010453:Peptide Synthases; C046746:cyclopeptide synthetase