6ofb: Difference between revisions
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<StructureSection load='6ofb' size='340' side='right'caption='[[6ofb]], [[Resolution|resolution]] 2.84Å' scene=''> | <StructureSection load='6ofb' size='340' side='right'caption='[[6ofb]], [[Resolution|resolution]] 2.84Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6ofb]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OFB FirstGlance]. <br> | <table><tr><td colspan='2'>[[6ofb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OFB FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ofc|6ofc]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ofc|6ofc]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NADSYN1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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=6ofb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofb OCA], [http://pdbe.org/6ofb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ofb RCSB], [http://www.ebi.ac.uk/pdbsum/6ofb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofb ProSAT]</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=6ofb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofb OCA], [http://pdbe.org/6ofb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ofb RCSB], [http://www.ebi.ac.uk/pdbsum/6ofb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofb ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://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> | [[http://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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ofb" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chuenchor, W]] | [[Category: Chuenchor, W]] | ||
Revision as of 19:40, 22 January 2020
Crystal structure of human glutamine-dependent NAD+ synthetase complexed with NaAD+, AMP, pyrophosphate, and Mg2+Crystal structure of human glutamine-dependent NAD+ synthetase complexed with NaAD+, AMP, pyrophosphate, and Mg2+
Structural highlights
Function[NADE_HUMAN] Catalyzes the ATP-dependent amidation of deamido-NAD to form NAD (PubMed:12547821). Uses L-glutamine as a nitrogen source (PubMed:12547821).[1] 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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