5nrz
From Proteopedia
(Difference between revisions)
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<StructureSection load='5nrz' size='340' side='right'caption='[[5nrz]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='5nrz' size='340' side='right'caption='[[5nrz]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5nrz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NRZ OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5nrz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus_Af293 Aspergillus fumigatus Af293]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NRZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NRZ FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> |
| - | <tr id=' | + | <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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=5nrz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nrz OCA], [https://pdbe.org/5nrz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nrz RCSB], [https://www.ebi.ac.uk/pdbsum/5nrz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nrz 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/GLIJ_ASPFU GLIJ_ASPFU] Dipeptidase; part of the gene cluster that mediates the biosynthesis of gliotoxin, a member of the epipolythiodioxopiperazine (ETP) class of toxins characterized by a disulfide bridged cyclic dipeptide (PubMed:15979823, PubMed:21612254). The first step in gliotoxin biosynthesis is the condensation of serine and phenylalanine to form the cyclo-L-phenylalanyl-L-serine diketopiperazine (DKP) by the NRPS gliP (PubMed:17154540, PubMed:21612254). GliP is also able to produce the DKP cyclo-L-tryptophanyl-L-serine, suggesting that the substrate specificity of the first adenylation (A) domain in gliP is sufficiently relaxed to accommodate both L-Phe and L-Trp (PubMed:23434416). The cytochrome P450 monooxygenase gliC has been shown to catalyze the subsequent hydroxylation of the alpha-carbon of L-Phe in cyclo-L-phenylalanyl-L-serine whereas the second cytochrome P450 enzyme, gliF, is presumably involved in the modification of the DKP side chain (PubMed:24039048, PubMed:23434416). The glutathione S-transferase (GST) gliG then forms a bis-glutathionylated biosynthetic intermediate which is responsible for the sulfurization of gliotoxin (PubMed:21513890, PubMed:21749092). This bis-glutathionylated intermediate is subsequently processed by the gamma-glutamyl cyclotransferase gliK to remove both gamma-glutamyl moieties (PubMed:22903976, PubMed:24039048). Subsequent processing via gliI yields a biosynthetic intermediate, which is N-methylated via the N-methyltransferase gliN, before the gliotoxin oxidoreductase gliT-mediated disulfide bridge closure (PubMed:20548963, PubMed:22936680, PubMed:24039048, PubMed:25062268). GliN-mediated amide methylation confers stability to ETP, damping the spontaneous formation of tri- and tetrasulfides (PubMed:25062268). Intracellular dithiol gliotoxin oxidized by gliT is subsequently effluxed by gliA (PubMed:26150413). Gliotoxin contributes to pathogenesis during invasive aspergillosis (PubMed:17601876, PubMed:18199036). In macrophages and neutrophils, gliotoxin showed inhibition of various different cell functions including cytokine production, antigen presentation, phagocytosis, and production of reactive oxygen species (PubMed:17601876).<ref>PMID:17154540</ref> <ref>PMID:18199036</ref> <ref>PMID:20548963</ref> <ref>PMID:21513890</ref> <ref>PMID:21612254</ref> <ref>PMID:21749092</ref> <ref>PMID:22903976</ref> <ref>PMID:22936680</ref> <ref>PMID:23434416</ref> <ref>PMID:24039048</ref> <ref>PMID:25062268</ref> |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Aspergillus fumigatus Af293]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | + | [[Category: Groll M]] | |
| - | [[Category: Groll | + | [[Category: Huber EM]] |
| - | [[Category: Huber | + | |
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Current revision
Cys-Gly dipeptidase GliJ in complex with Mn2+
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