View source for 6ofb


==Crystal structure of human glutamine-dependent NAD+ synthetase complexed with NaAD+, AMP, pyrophosphate, and Mg2+==
<StructureSection load='6ofb' size='340' side='right'caption='[[6ofb]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ofb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OFB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OFB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.84&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DND:NICOTINIC+ACID+ADENINE+DINUCLEOTIDE'>DND</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ofb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofb OCA], [https://pdbe.org/6ofb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ofb RCSB], [https://www.ebi.ac.uk/pdbsum/6ofb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NADE_HUMAN NADE_HUMAN] Catalyzes the ATP-dependent amidation of deamido-NAD to form NAD (PubMed:12547821). Uses L-glutamine as a nitrogen source (PubMed:12547821).<ref>PMID:12547821</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:31911602</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ofb" style="background-color:#fffaf0;"></div>

==See Also==
*[[NAD synthase|NAD synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chuenchor W]]
[[Category: Doukov TI]]
[[Category: Gerratana B]]