3DLA

X-ray crystal structure of glutamine-dependent NAD+ synthetase from Mycobacterium tuberculosis bound to NaAD+ and DON

Summary for 3DLA

• Entry DOI: 10.2210/pdb3dla/pdb
• Descriptor: Glutamine-dependent NAD(+) synthetase, NICOTINIC ACID ADENINE DINUCLEOTIDE, 5-OXO-L-NORLEUCINE, ... (5 entities in total)
• Functional Keywords: glutaminase, nad+ synthetase, ammonia tunneling, enzyme, glutamine-dependent nad+ synthetase, glutamine-amido transferase, atp-binding, ligase, nad, nucleotide-binding
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 4
• Total formula weight: 304045.36

Authors

LaRonde-LeBlanc, N.A.,Resto, M.,Gerratana, B. (deposition date: 2008-06-26, release date: 2009-03-10, Last modification date: 2019-10-23)

Primary citation

LaRonde-LeBlanc, N.,Resto, M.,Gerratana, B.
Regulation of active site coupling in glutamine-dependent NAD(+) synthetase.
Nat.Struct.Mol.Biol., 16:421-429, 2009

PubMed 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.

PubMed: 19270703
DOI: 10.1038/nsmb.1567

Experimental method

X-RAY DIFFRACTION (2.35 Å)