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| | ==Structure of glycosylated glutaminyl cyclase from Drosophila melanogaster== | | ==Structure of glycosylated glutaminyl cyclase from Drosophila melanogaster== |
| - | <StructureSection load='4f9u' size='340' side='right' caption='[[4f9u]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='4f9u' size='340' side='right'caption='[[4f9u]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4f9u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F9U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F9U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4f9u]] is a 2 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=4F9U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F9U FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PBD:1-(3,4-DIMETHOXYPHENYL)-3-[3-(1H-IMIDAZOL-1-YL)PROPYL]THIOUREA'>PBD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3si2|3si2]], [[4f9v|4f9v]], [[4fai|4fai]], [[4fbe|4fbe]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PBD:1-(3,4-DIMETHOXYPHENYL)-3-[3-(1H-IMIDAZOL-1-YL)PROPYL]THIOUREA'>PBD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">QC, CG10487, CG32412, Dmel_CG32412 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</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=4f9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f9u OCA], [https://pdbe.org/4f9u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f9u RCSB], [https://www.ebi.ac.uk/pdbsum/4f9u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f9u 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=4f9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f9u OCA], [http://pdbe.org/4f9u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f9u RCSB], [http://www.ebi.ac.uk/pdbsum/4f9u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f9u ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/QPCT1_DROME QPCT1_DROME] Acts as a glutaminyl-peptide cyclotransferase (PubMed:17722885, PubMed:22897232). Responsible for the biosynthesis of pyroglutamyl peptides (By similarity). Might be more efficient in the conversion of tri and tetrapeptides in vitro (PubMed:17722885). Might have a relative preference for substrates containing hydrophobic amino acids in vitro (PubMed:17722885).[UniProtKB:Q16769]<ref>PMID:17722885</ref> <ref>PMID:22897232</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4f9u" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4f9u" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glutaminyl cyclase|Glutaminyl cyclase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Drome]] | + | [[Category: Drosophila melanogaster]] |
| - | [[Category: Koch, B]] | + | [[Category: Large Structures]] |
| - | [[Category: Kolenko, P]] | + | [[Category: Koch B]] |
| - | [[Category: Ruiz-Carilo, D]] | + | [[Category: Kolenko P]] |
| - | [[Category: Stubbs, M T]] | + | [[Category: Ruiz-Carilo D]] |
| - | [[Category: Alpha/beta hydrolase]]
| + | [[Category: Stubbs MT]] |
| - | [[Category: Alzheimer's disease]]
| + | |
| - | [[Category: Glycosylation]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Pe]]
| + | |
| - | [[Category: Pglu formation]]
| + | |
| - | [[Category: Pglu-amyloid]]
| + | |
| - | [[Category: Pyroglutamate]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
4f9u is a 2 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.8Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
QPCT1_DROME Acts as a glutaminyl-peptide cyclotransferase (PubMed:17722885, PubMed:22897232). Responsible for the biosynthesis of pyroglutamyl peptides (By similarity). Might be more efficient in the conversion of tri and tetrapeptides in vitro (PubMed:17722885). Might have a relative preference for substrates containing hydrophobic amino acids in vitro (PubMed:17722885).[UniProtKB:Q16769][1] [2]
Publication Abstract from PubMed
Glutaminyl cyclases (QCs), which catalyze the formation of pyroglutamic acid (pGlu) at the N-terminus of a variety of peptides and proteins, have attracted particular attention for their potential role in Alzheimer's disease. In a transgenic Drosophila melanogaster (Dm) fruit fly model, oral application of the potent competitive QC inhibitor PBD150 was shown to reduce the burden of pGlu-modified Abeta. In contrast to mammals such as humans and rodents, there are at least three DmQC species, one of which (isoDromeQC) is localized to mitochondria, whereas DromeQC and an isoDromeQC splice variant possess signal peptides for secretion. Here we present the recombinant expression, characterization and crystal structure determination of mature DromeQC and isoDromeQC, revealing a similar overall fold to mammalian QCs. In the case of isoDromeQC, the putative extended substrate binding site might be affected by proximity of the N-terminal residues. PBD150 inhibition of DromeQC is roughly one order of magnitude lower than that of the human and murine QCs. The inhibitor binds to isoDromeQC in a similar fashion to that observed for human QCs, whereas it adopts alternative binding modes in a DromeQC variant lacking the conserved cysteines near to the active center and shows a disordered dimethoxyphenyl moiety in wild type DromeQC, providing an explanation for the lower affinity. Our biophysical and structural data suggest that isoDromeQC and human QC are similar with regard to functional aspects. The two Dm enzymes represent a suitable model for further in depth analysis of the catalytic mechanism of animal QCs, and isoDromeQC might serve as a model system for structure based design of potential AD therapeutics.
Crystal Structures of Glutaminyl Cyclases from Drosophila melanogaster Reveal Active Site Conservation between Insect and Mammalian QCs.,Koch B, Kolenko P, Buchholz M, Ruiz Carrillo D, Parthier C, Wermann M, Rahfeld JU, Reuter G, Schilling S, Stubbs MT, Demuth HU Biochemistry. 2012 Aug 16. PMID:22897232[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schilling S, Lindner C, Koch B, Wermann M, Rahfeld JU, von Bohlen A, Rudolph T, Reuter G, Demuth HU. Isolation and characterization of glutaminyl cyclases from Drosophila: evidence for enzyme forms with different subcellular localization. Biochemistry. 2007 Sep 25;46(38):10921-30. PMID:17722885 doi:10.1021/bi701043x
- ↑ Koch B, Kolenko P, Buchholz M, Ruiz Carrillo D, Parthier C, Wermann M, Rahfeld JU, Reuter G, Schilling S, Stubbs MT, Demuth HU. Crystal Structures of Glutaminyl Cyclases from Drosophila melanogaster Reveal Active Site Conservation between Insect and Mammalian QCs. Biochemistry. 2012 Aug 16. PMID:22897232 doi:10.1021/bi300687g
- ↑ Koch B, Kolenko P, Buchholz M, Ruiz Carrillo D, Parthier C, Wermann M, Rahfeld JU, Reuter G, Schilling S, Stubbs MT, Demuth HU. Crystal Structures of Glutaminyl Cyclases from Drosophila melanogaster Reveal Active Site Conservation between Insect and Mammalian QCs. Biochemistry. 2012 Aug 16. PMID:22897232 doi:10.1021/bi300687g
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