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| | <StructureSection load='7nsz' size='340' side='right'caption='[[7nsz]], [[Resolution|resolution]] 1.30Å' scene=''> | | <StructureSection load='7nsz' size='340' side='right'caption='[[7nsz]], [[Resolution|resolution]] 1.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7nsz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NSZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NSZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7nsz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NSZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NSZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PGRP-LB, CG14704 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/N-acetylmuramoyl-L-alanine_amidase N-acetylmuramoyl-L-alanine amidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.28 3.5.1.28] </span></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=7nsz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nsz OCA], [https://pdbe.org/7nsz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nsz RCSB], [https://www.ebi.ac.uk/pdbsum/7nsz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nsz ProSAT]</span></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=7nsz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nsz OCA], [https://pdbe.org/7nsz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nsz RCSB], [https://www.ebi.ac.uk/pdbsum/7nsz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nsz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PGPLB_DROME PGPLB_DROME]] N-acetylmuramyl-L-alanine amidase involved in innate immunity by degrading bacterial peptidoglycans (PGN). Probably plays a scavenger role by digesting biologically active PGN into biologically inactive fragments. Has no direct bacteriolytic activity.<ref>PMID:12845326</ref>
| + | [https://www.uniprot.org/uniprot/PGPLB_DROME PGPLB_DROME] N-acetylmuramyl-L-alanine amidase involved in innate immunity by degrading bacterial peptidoglycans (PGN). Probably plays a scavenger role by digesting biologically active PGN into biologically inactive fragments. Has no direct bacteriolytic activity.<ref>PMID:12845326</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: Drome]] | + | [[Category: Drosophila melanogaster]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: N-acetylmuramoyl-L-alanine amidase]]
| + | [[Category: Aller P]] |
| - | [[Category: Aller, P]] | + | [[Category: Da Silva P]] |
| - | [[Category: Orlans, J]] | + | [[Category: Orlans J]] |
| - | [[Category: Silva, P Da]]
| + | |
| - | [[Category: Drosophila]] | + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Peptidoglycan recognition protein]]
| + | |
| - | [[Category: Pgrp]]
| + | |
| - | [[Category: Pgrp-lb]]
| + | |
| Structural highlights
Function
PGPLB_DROME N-acetylmuramyl-L-alanine amidase involved in innate immunity by degrading bacterial peptidoglycans (PGN). Probably plays a scavenger role by digesting biologically active PGN into biologically inactive fragments. Has no direct bacteriolytic activity.[1]
Publication Abstract from PubMed
Peptidoglycan recognition proteins (PGRPs) are ubiquitous among animals and play pivotal functions in insect immunity. Non-catalytic PGRPs are involved in the activation of immune pathways by binding to the peptidoglycan (PGN), whereas amidase PGRPs are capable of cleaving the PGN into non-immunogenic compounds. Drosophila PGRP-LB belongs to the amidase PGRPs and downregulates the immune deficiency (IMD) pathway by cleaving meso-2,6-diaminopimelic (meso-DAP or DAP)-type PGN. While the recognition process is well analyzed for the non-catalytic PGRPs, little is known about the enzymatic mechanism for the amidase PGRPs, despite their essential function in immune homeostasis. Here, we analyzed the specific activity of different isoforms of Drosophila PGRP-LB towards various PGN substrates to understand their specificity and role in Drosophila immunity. We show that these isoforms have similar activity towards the different compounds. To analyze the mechanism of the amidase activity, we performed site directed mutagenesis and solved the X-ray structures of wild-type Drosophila PGRP-LB and its mutants, with one of these structures presenting a protein complexed with the tracheal cytotoxin (TCT), a muropeptide derived from the PGN. Only the Y78F mutation abolished the PGN cleavage while other mutations reduced the activity solely. Together, our findings suggest the dynamic role of the residue Y78 in the amidase mechanism by nucleophilic attack through a water molecule to the carbonyl group of the amide function destabilized by Zn(2+).
PGRP-LB: An Inside View into the Mechanism of the Amidase Reaction.,Orlans J, Vincent-Monegat C, Rahioui I, Sivignon C, Butryn A, Soulere L, Zaidman-Remy A, Orville AM, Heddi A, Aller P, Da Silva P Int J Mol Sci. 2021 May 7;22(9). pii: ijms22094957. doi: 10.3390/ijms22094957. PMID:34066955[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kim MS, Byun M, Oh BH. Crystal structure of peptidoglycan recognition protein LB from Drosophila melanogaster. Nat Immunol. 2003 Aug;4(8):787-93. Epub 2003 Jul 6. PMID:12845326 doi:10.1038/ni952
- ↑ Orlans J, Vincent-Monegat C, Rahioui I, Sivignon C, Butryn A, Soulere L, Zaidman-Remy A, Orville AM, Heddi A, Aller P, Da Silva P. PGRP-LB: An Inside View into the Mechanism of the Amidase Reaction. Int J Mol Sci. 2021 May 7;22(9). pii: ijms22094957. doi: 10.3390/ijms22094957. PMID:34066955 doi:http://dx.doi.org/10.3390/ijms22094957
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