6OFC

Crystal structure of M. tuberculosis glutamine-dependent NAD+ synthetase complexed with Sulfonamide derivative 1, pyrophosphate, and glutamine

Summary for 6OFC

• Entry DOI: 10.2210/pdb6ofc/pdb
• Related: 6OFB
• Descriptor: Glutamine-dependent NAD(+) synthetase, 5'-O-[(pyridine-3-carbonyl)sulfamoyl]adenosine, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: ligase, glutamine-amido transferase, gat, nad+ synthetase, glutamine-dependent nad+ synthetase, nad synthetase 1, glutaminase, ammonia tunneling, enzyme, atp-binding, nucleotide-binding, inhibitor complex, tuberculosis
• Biological source: Mycobacterium tuberculosis CDC1551
• Total number of polymer chains: 4
• Total formula weight: 303496.79

Authors

Chuenchor, W.,Doukov, T.I.,Gerratana, B. (deposition date: 2019-03-28, release date: 2020-01-08, Last modification date: 2023-10-25)

Primary citation

Chuenchor, W.,Doukov, T.I.,Chang, K.T.,Resto, M.,Yun, C.S.,Gerratana, B.
Different ways to transport ammonia in human and Mycobacterium tuberculosis NAD+synthetases.
Nat Commun, 11:16-16, 2020

PubMed Abstract: NAD synthetase is an essential enzyme of de novo and recycling pathways of NAD biosynthesis in Mycobacterium tuberculosis but not in humans. This bifunctional enzyme couples the NAD synthetase and glutaminase activities through an ammonia tunnel but free ammonia is also a substrate. Here we show that the Homo sapiens NAD synthetase (hsNadE) lacks substrate specificity for glutamine over ammonia and displays a modest activation of the glutaminase domain compared to tbNadE. We report the crystal structures of hsNadE and NAD synthetase from M. tuberculosis (tbNadE) with synthetase intermediate analogues. Based on the observed exclusive arrangements of the domains and of the intra- or inter-subunit tunnels we propose a model for the inter-domain communication mechanism for the regulation of glutamine-dependent activity and NH transport. The structural and mechanistic comparison herein reported between hsNadE and tbNadE provides also a starting point for future efforts in the development of anti-TB drugs.

PubMed: 31911602
DOI: 10.1038/s41467-019-13845-4

Experimental method

X-RAY DIFFRACTION (3.14 Å)