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J Mol Biol. 2003 May 16;328(5):985-94.

Crystal structure of the human CCA-adding enzyme: insights into template-independent polymerization.

Author information

1
Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18A, D-82152 Martinsried, Germany. augustin@biochem.mpg.de

Abstract

All tRNA molecules carry the invariant sequence CCA at their 3'-terminus for amino acid attachment. The post-transcriptional addition of CCA is carried out by ATP(CTP):tRNA nucleotidyltransferase, also called CCase. This enzyme catalyses a unique template-independent but sequence-specific nucleotide polymerization reaction. In order to reveal the molecular mechanism of this activity, we solved the crystal structure of human CCase by single isomorphous replacement. The structure reveals a four domain architecture with a cluster of conserved residues forming a positively charged cleft between the first two domains. Structural homology of the N-terminal CCase domain to other nucleotidyltransferases could be exploited for modeling a tRNA-substrate complex. The model places the tRNA 3'-end into the N-terminal nucleotidyltransferase site, close to a patch of conserved residues that provide the binding sites for CTP and ATP. Based on our results, we introduce a corkscrew model for CCA addition that includes a fixed active site and a traveling tRNA-binding region formed by flexible parts of the protein.

PMID:
12729736
DOI:
10.1016/s0022-2836(03)00381-4
[Indexed for MEDLINE]

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