The structure and mechanism of the Mycobacterium tuberculosis cyclodityrosine synthetase

被引:54
作者
Vetting, Matthew W. [1 ]
Hegde, Subray S. [1 ]
Blanchard, John S. [1 ]
机构
[1] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10467 USA
基金
美国国家卫生研究院;
关键词
BIOSYNTHETIC GENE-CLUSTER; ASPERGILLUS-FUMIGATUS; IN-VITRO; PEPTIDE; CYTOCHROME-P450; GLIOTOXIN; CYP121; VIVO;
D O I
10.1038/NCHEMBIO.440
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-angstrom 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.
引用
收藏
页码:797 / 799
页数:3
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