The Nudix hydrolase CDP-chase, a CDP-choline pyrophosphatase, is an asymmetric dimer with two distinct enzymatic activities

Krisna C. Duong-Ly, Sandra B. Gabelli, Wen Lian Xu, Christopher A. Dunn, Andrew J. Schoeffield, Maurice J. Bessman, L. Mario Amzel

Research output: Contribution to journalArticlepeer-review

Abstract

A Nudix enzyme from Bacillus cereus (NCBI RefSeq accession no. NP_831800) catalyzes the hydrolysis of CDP-choline to produce CMP and phosphocholine. Here, we show that in addition, the enzyme has a 3'→5' RNA exonuclease activity. The structure of the free enzyme, determined to a 1.8-Å resolution, shows that the enzyme is an asymmetric dimer. Each monomer consists of two domains, an N-terminal helical domain and a C-terminal Nudix domain. The N-terminal domain is placed relative to the C-terminal domain such as to result in an overall asymmetric arrangement with two distinct catalytic sites: one with an "enclosed" Nudix pyrophosphatase site and the other with a more open, less-defined cavity. Residues that may be important for determining the asymmetry are conserved among a group of uncharacterized Nudix enzymes from Gram-positive bacteria. Our data support a model where CDP-choline hydrolysis is catalyzed by the enclosed Nudix site and RNA exonuclease activity is catalyzed by the open site. CDPChase is the first identified member of a novel Nudix family in which structural asymmetry has a profound effect on the recognition of substrates.

Original languageEnglish (US)
Pages (from-to)3175-3185
Number of pages11
JournalJournal of bacteriology
Volume193
Issue number13
DOIs
StatePublished - Jul 2011

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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