8r17
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Neurospora crassa NADase with modified C-terminus== | |
| + | <StructureSection load='8r17' size='340' side='right'caption='[[8r17]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8r17]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus_Af293 Aspergillus fumigatus Af293] and [https://en.wikipedia.org/wiki/Neurospora_crassa Neurospora crassa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8R17 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8R17 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]] 2.3Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=8r17 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8r17 OCA], [https://pdbe.org/8r17 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8r17 RCSB], [https://www.ebi.ac.uk/pdbsum/8r17 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8r17 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NADA_NEUCR NADA_NEUCR] Conidial surface nicotinamide adenine dinucleotide glycohydrolase that cleave NAD(+) and NADP(+) but not their reduced counterparts, NADH and NADPH (PubMed:33712585, PubMed:6260480). Lacks both ADP-ribosyl cyclase and base exchange activity and does not mediate synthesis of calcium messengers cADPR or NAADP (PubMed:33712585). Its function is correlated with aerial hyphae formation and conidiogenesis, but its physiological role is still obscure (PubMed:131723, PubMed:165174). Is able to ADP-ribosylate itself for self-inactivation (PubMed:9787786).<ref>PMID:131723</ref> <ref>PMID:165174</ref> <ref>PMID:33712585</ref> <ref>PMID:6260480</ref> <ref>PMID:9787786</ref> [https://www.uniprot.org/uniprot/NADA_ASPFU NADA_ASPFU] Conidial surface nicotinamide adenine dinucleotide glycohydrolase that cleave NAD(+) and NADP(+) but not their reduced counterparts, NADH and NADPH (PubMed:33712585). Lacks both ADP-ribosyl cyclase and base exchange activity and does not mediate synthesis of calcium messengers cADPR or NAADP (PubMed:33712585). Plays a role in pathogenicity by depleting the host's NAD(+) pool (PubMed:33712585).<ref>PMID:33712585</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Tuberculosis necrotizing toxin (TNT) is a protein domain discovered on the outer membrane of Mycobacterium tuberculosis (Mtb), and the fungal pathogen Aspergillus fumigatus. TNT domains have pure NAD(P) hydrolytic activity, setting them apart from other NAD-cleaving domains such as ADP-ribosyl cyclase and Toll/interleukin-1 receptor homology (TIR) domains which form a wider set of products. Importantly, the Mtb TNT domain has been shown to be involved in immune evasion via depletion of the intracellular NAD pool of macrophages. Therefore, an intriguing hypothesis is that TNT domains act as "NAD killers" in host cells facilitating pathogenesis. Here, we explore the phylogenetic distribution of TNT domains and detect their presence solely in bacteria and fungi. Within fungi, we discerned six TNT clades. In addition, X-ray crystallography and AlphaFold2 modeling unveiled clade-specific strategies to promote homodimer stabilization of the fungal enzymes, namely, Ca(2+) binding, disulfide bonds, or hydrogen bonds. We show that dimer stabilization is a requirement for NADase activity and that the group-specific strategies affect the active site conformation, thereby modulating enzyme activity. Together, these findings reveal the evolutionary lineage of fungal TNT enzymes, corroborating the hypothesis of them being pure extracellular NAD (eNAD) cleavers, with possible involvement in microbial warfare and host immune evasion. | ||
| - | + | Evolution of fungal tuberculosis necrotizing toxin (TNT) domain-containing enzymes reveals divergent adaptations to enhance NAD cleavage.,Ferrario E, Kallio JP, Emdadi M, Stromland O, Rack JGM, Ziegler M Protein Sci. 2024 Jul;33(7):e5071. doi: 10.1002/pro.5071. PMID:38895984<ref>PMID:38895984</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8r17" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: Ferrario | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Aspergillus fumigatus Af293]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Neurospora crassa]] | ||
| + | [[Category: Ferrario E]] | ||
| + | [[Category: Kallio JP]] | ||
| + | [[Category: Ziegler M]] | ||
Current revision
Crystal structure of Neurospora crassa NADase with modified C-terminus
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