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Nat Struct Mol Biol. 2009 Apr;16(4):421-9. doi: 10.1038/nsmb.1567. Epub 2009 Mar 8.

Regulation of active site coupling in glutamine-dependent NAD(+) synthetase.

Author information

1
Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742-2021, USA. nlaronde@umd.edu

Abstract

NAD(+) is an essential metabolite both as a cofactor in energy metabolism and redox homeostasis and as a regulator of cellular processes. In contrast to humans, Mycobacterium tuberculosis NAD(+) biosynthesis is absolutely dependent on the activity of a multifunctional glutamine-dependent NAD(+) synthetase, which catalyzes the ATP-dependent formation of NAD(+) at the synthetase domain using ammonia derived from L-glutamine in the glutaminase domain. Here we report the kinetics and structural characterization of M. tuberculosis NAD(+) synthetase. The kinetics data strongly suggest tightly coupled regulation of the catalytic activities. The structure, the first of a glutamine-dependent NAD(+) synthetase, reveals a homooctameric subunit organization suggesting a tight dependence of catalysis on the quaternary structure, a 40-A intersubunit ammonia tunnel and structural elements that may be involved in the transfer of information between catalytic sites.

PMID:
19270703
DOI:
10.1038/nsmb.1567
[Indexed for MEDLINE]

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