Bifunctional NMN Adenylyltransferase/ADP-Ribose Pyrophosphatase: Structure and Function in Bacterial NAD Metabolism

Nian Huang, Leonardo Sorci, Xuejun Zhang, Chad A Brautigam, Xiaoqing Li, Nadia Raffaelli, Giulio Magni, Nick V Grishin, Andrei L. Osterman, Hong Zhang

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Bacterial NadM-Nudix is a bifunctional enzyme containing a nicotinamide mononucleotide (NMN) adenylyltransferase and an ADP-ribose (ADPR) pyrophosphatase domain. While most members of this enzyme family, such as that from a model cyanobacterium Synechocystis sp., are involved primarily in nicotinamide adenine dinucleotide (NAD) salvage/recycling pathways, its close homolog in a category-A biodefense pathogen, Francisella tularensis, likely plays a central role in a recently discovered novel pathway of NAD de novo synthesis. The crystal structures of NadM-Nudix from both species, including their complexes with various ligands and catalytic metal ions, revealed detailed configurations of the substrate binding and catalytic sites in both domains. The structure of the N-terminal NadM domain may be exploited for designing new antitularemia therapeutics. The ADPR binding site in the C-terminal Nudix domain is substantially different from that of Escherichia coli ADPR pyrophosphatase, and is more similar to human NUDT9. The latter observation provided new insights into the ligand binding mode of ADPR-gated Ca2+ channel TRPM2.

Original languageEnglish (US)
Pages (from-to)196-209
Number of pages14
JournalStructure
Volume16
Issue number2
DOIs
StatePublished - Feb 12 2008

Keywords

  • MICROBIO
  • PROTEINS

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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