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| | ==Structure of glycosylated murine glutaminyl cyclase in presence of the inhibitor PQ50 (PDBD150)== | | ==Structure of glycosylated murine glutaminyl cyclase in presence of the inhibitor PQ50 (PDBD150)== |
| - | <StructureSection load='3si2' size='340' side='right' caption='[[3si2]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='3si2' size='340' side='right'caption='[[3si2]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3si2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SI2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SI2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3si2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SI2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=SO4:SULFATE+ION'>SO4</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]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3si1|3si1]], [[3si0|3si0]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=PRD_900017:triacetyl-beta-chitotriose'>PRD_900017</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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">Qpct ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3si2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3si2 OCA], [https://pdbe.org/3si2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3si2 RCSB], [https://www.ebi.ac.uk/pdbsum/3si2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3si2 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutaminyl-peptide_cyclotransferase Glutaminyl-peptide cyclotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.5 2.3.2.5] </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=3si2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3si2 OCA], [http://pdbe.org/3si2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3si2 RCSB], [http://www.ebi.ac.uk/pdbsum/3si2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3si2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/QPCT_MOUSE QPCT_MOUSE] Responsible for the biosynthesis of pyroglutamyl peptides. Has a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue (By similarity). |
| | <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 3si2" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3si2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glutaminyl cyclase|Glutaminyl cyclase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glutaminyl-peptide cyclotransferase]] | + | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Carrillo, D]] | + | [[Category: Carrillo D]] |
| - | [[Category: Parthier, C]] | + | [[Category: Parthier C]] |
| - | [[Category: Stubbs, M T]] | + | [[Category: Stubbs MT]] |
| - | [[Category: Alpha/beta hydrolase]]
| + | |
| - | [[Category: Alzheimer's disease]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Glycosylation]]
| + | |
| - | [[Category: Pe]]
| + | |
| - | [[Category: Pglu]]
| + | |
| - | [[Category: Pglu-amyloid]]
| + | |
| - | [[Category: Pyroglutamate]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
3si2 is a 1 chain structure with sequence from Mus musculus. 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
QPCT_MOUSE Responsible for the biosynthesis of pyroglutamyl peptides. Has a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue (By similarity).
Publication Abstract from PubMed
Formation of N-terminal pyroglutamate (pGlu or pE) from glutaminyl or glutamyl precursors is catalyzed by glutaminyl cyclases (QC). As the formation of pGlu-amyloid has been linked with Alzheimer's disease, inhibitors of QCs are currently the subject of intense development. Here, we report three crystal structures of N-glycosylated mammalian QC from humans (hQC) and mice (mQC). Whereas the overall structures of the enzymes are similar to those reported previously, two surface loops in the neighborhood of the active center exhibit conformational variability. Furthermore, two conserved cysteine residues form a disulfide bond at the base of the active center that was not present in previous reports of hQC structure. Site-directed mutagenesis suggests a structure-stabilizing role of the disulfide bond. At the entrance to the active center, the conserved tryptophan residue, W(207), which displayed multiple orientations in previous structure, shows a single conformation in both glycosylated human and murine QCs. Although mutagenesis of W(207) into leucine or glutamine altered substrate conversion significantly, the binding constants of inhibitors such as the highly potent PQ50 (PBD150) were minimally affected. The crystal structure of PQ50 bound to the active center of murine QC reveals principal binding determinants provided by the catalytic zinc ion and a hydrophobic funnel. This study presents a first comparison of two mammalian QCs containing typical, conserved post-translational modifications.
Structures of Glycosylated Mammalian Glutaminyl Cyclases Reveal Conformational Variability near the Active Center.,Ruiz-Carrillo D, Koch B, Parthier C, Wermann M, Dambe T, Buchholz M, Ludwig HH, Heiser U, Rahfeld JU, Stubbs MT, Schilling S, Demuth HU Biochemistry. 2011 Jun 27. PMID:21671571[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ruiz-Carrillo D, Koch B, Parthier C, Wermann M, Dambe T, Buchholz M, Ludwig HH, Heiser U, Rahfeld JU, Stubbs MT, Schilling S, Demuth HU. Structures of Glycosylated Mammalian Glutaminyl Cyclases Reveal Conformational Variability near the Active Center. Biochemistry. 2011 Jun 27. PMID:21671571 doi:10.1021/bi200249h
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