View source for 6ofc


==Crystal structure of M. tuberculosis glutamine-dependent NAD+ synthetase complexed with Sulfonamide derivative 1, pyrophosphate, and glutamine==
<StructureSection load='6ofc' size='340' side='right'caption='[[6ofc]], [[Resolution|resolution]] 3.14&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ofc]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycto Mycto]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OFC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GLN:GLUTAMINE'>GLN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene>, <scene name='pdbligand=SFH:5-O-[(pyridine-3-carbonyl)sulfamoyl]adenosine'>SFH</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ofb|6ofb]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">nadE, MT2513 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83331 MYCTO])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_synthase_(glutamine-hydrolyzing) NAD(+) synthase (glutamine-hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.5.1 6.3.5.1] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ofc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofc OCA], [http://pdbe.org/6ofc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ofc RCSB], [http://www.ebi.ac.uk/pdbsum/6ofc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofc ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/NADE_MYCTO NADE_MYCTO]] Catalyzes the ATP-dependent amidation of deamido-NAD to form NAD. Uses L-glutamine as a nitrogen source.[HAMAP-Rule:MF_02090] 
<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 6ofc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycto]]
[[Category: Chuenchor, W]]
[[Category: Doukov, T I]]
[[Category: Gerratana, B]]
[[Category: Ammonia tunneling]]
[[Category: Atp-binding]]
[[Category: Enzyme]]
[[Category: Gat]]
[[Category: Glutaminase]]
[[Category: Glutamine-amido transferase]]
[[Category: Glutamine-dependent nad+ synthetase]]
[[Category: Inhibitor complex]]
[[Category: Ligase]]
[[Category: Nad synthetase 1]]
[[Category: Nad+ synthetase]]
[[Category: Nucleotide-binding]]
[[Category: Tuberculosis]]