Structural highlights
6ofc is a 4 chain structure with sequence from Mycto. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , |
| Related: | 6ofb |
| Gene: | nadE, MT2513 (MYCTO) |
| Activity: | NAD(+) synthase (glutamine-hydrolyzing), with EC number 6.3.5.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[NADE_MYCTO] Catalyzes the ATP-dependent amidation of deamido-NAD to form NAD. Uses L-glutamine as a nitrogen source.[HAMAP-Rule:MF_02090]
Publication Abstract from PubMed
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 NH3 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.
Different ways to transport ammonia in human and Mycobacterium tuberculosis NAD(+) synthetases.,Chuenchor W, Doukov TI, Chang KT, Resto M, Yun CS, Gerratana B Nat Commun. 2020 Jan 7;11(1):16. doi: 10.1038/s41467-019-13845-4. PMID:31911602[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chuenchor W, Doukov TI, Chang KT, Resto M, Yun CS, Gerratana B. Different ways to transport ammonia in human and Mycobacterium tuberculosis NAD(+) synthetases. Nat Commun. 2020 Jan 7;11(1):16. doi: 10.1038/s41467-019-13845-4. PMID:31911602 doi:http://dx.doi.org/10.1038/s41467-019-13845-4
