6ofc: Difference between revisions
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<StructureSection load='6ofc' size='340' side='right'caption='[[6ofc]], [[Resolution|resolution]] 3.14Å' scene=''> | <StructureSection load='6ofc' size='340' side='right'caption='[[6ofc]], [[Resolution|resolution]] 3.14Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6ofc]] is a 4 chain structure. 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 [ | <table><tr><td colspan='2'>[[6ofc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. 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 [https://proteopedia.org/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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.14Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ofc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofc OCA], [https://pdbe.org/6ofc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ofc RCSB], [https://www.ebi.ac.uk/pdbsum/6ofc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofc ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ofc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[NAD synthase|NAD synthase]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mycobacterium tuberculosis CDC1551]] | ||
[[Category: | [[Category: Chuenchor W]] | ||
[[Category: | [[Category: Doukov TI]] | ||
[[Category: | [[Category: Gerratana B]] | ||
Latest revision as of 12:15, 25 October 2023
Crystal structure of M. tuberculosis glutamine-dependent NAD+ synthetase complexed with Sulfonamide derivative 1, pyrophosphate, and glutamineCrystal structure of M. tuberculosis glutamine-dependent NAD+ synthetase complexed with Sulfonamide derivative 1, pyrophosphate, and glutamine
Structural highlights
FunctionNADE_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 PubMedNAD(+) 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. See AlsoReferences
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