Crystal structures of E. coli nicotinate mononucleotide adenylyltransferase and its complex with deamido-NAD

Hong Zhang, Tianjun Zhou, Oleg Kurnasov, Sara Cheek, Nick V. Grishin, Andrei Osterman

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Nicotinamide/Nicotinate mononucleotide (NMN/NaMN) adenylyltransferase is an indispensable enzyme in both de novo biosynthesis and salvage of NAD+ and NADP+. In prokaryotes, it is absolutely required for cell survival, thus representing an attractive target for the development of new broad-spectrum antibacteria inhibitors. The crystal structures of E. coli NaMN adenylyltransferase (NMNAT) and its complex with deamido-NAD (NaAD) revealed that ligand binding causes large conformational changes in several loop regions around the active site. The enzyme specifically recognizes the deamidated pyridine nucleotide through interactions between nicotinate carboxylate with several protein main chain amides and a positive helix dipole. Comparison of E. coli NMNAT with those from archaeal organisms revealed extensive differences in the active site architecture, enzyme-ligand interaction mode, and bound dinucleotide conformations. The bacterial NaMN adenylyltransferase structures described here provide a foundation for structure-based design of specific inhibitors that may have therapeutic potential.

Original languageEnglish (US)
Pages (from-to)69-79
Number of pages11
JournalStructure
Volume10
Issue number1
DOIs
StatePublished - Feb 11 2002

Keywords

  • Adenylyltransferase
  • Antibacteria
  • Crystal structure
  • NAD
  • Nicotinate monophosphate nucleotide
  • Nucleotidyltransferase superfamily

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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