3pbb: Difference between revisions

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-[[Image:3pbb.png|left|200px]]
+==Crystal structure of human secretory glutaminyl cyclase in complex with PBD150==
+<StructureSection load='3pbb' size='340' side='right' caption='[[3pbb]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3pbb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PBB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PBB FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2afm|2afm]], [[3pb4|3pb4]], [[3pb6|3pb6]], [[3pb7|3pb7]], [[3pb8|3pb8]], [[3pb9|3pb9]], [[3pbe|3pbe]]</td></tr>
+<tr><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=9606 Homo sapiens])</td></tr>
+<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3pbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pbb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pbb RCSB], [http://www.ebi.ac.uk/pdbsum/3pbb PDBsum]</span></td></tr>
+<table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Aberrant pyroglutamate formation at the N terminus of certain peptides and proteins, catalyzed by glutaminyl cyclases (QCs), is linked to some pathological conditions, such as Alzheimer disease. Recently, a glutaminyl cyclase (QC) inhibitor, PBD150, was shown to be able to reduce the deposition of pyroglutamate-modified amyloid-beta peptides in brain of transgenic mouse models of Alzheimer disease, leading to a significant improvement of learning and memory in those transgenic animals. Here, we report the 1.05-1.40 A resolution structures, solved by the sulfur single-wavelength anomalous dispersion phasing method, of the Golgi-luminal catalytic domain of the recently identified Golgi-resident QC (gQC) and its complex with PBD150. We also describe the high-resolution structures of secretory QC (sQC)-PBD150 complex and two other gQC-inhibitor complexes. gQC structure has a scaffold similar to that of sQC but with a relatively wider and negatively charged active site, suggesting a distinct substrate specificity from sQC. Upon binding to PBD150, a large loop movement in gQC allows the inhibitor to be tightly held in its active site primarily by hydrophobic interactions. Further comparisons of the inhibitor-bound structures revealed distinct interactions of the inhibitors with gQC and sQC, which are consistent with the results from our inhibitor assays reported here. Because gQC and sQC may play different biological roles in vivo, the different inhibitor binding modes allow the design of specific inhibitors toward gQC and sQC.
-<!--
+Structures of human Golgi-resident glutaminyl cyclase and its complexes with inhibitors reveal a large loop movement upon inhibitor binding.,Huang KF, Liaw SS, Huang WL, Chia CY, Lo YC, Chen YL, Wang AH J Biol Chem. 2011 Apr 8;286(14):12439-49. Epub 2011 Feb 1. PMID:21288892<ref>PMID:21288892</ref>
-The line below this paragraph, containing "STRUCTURE_3pbb", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_3pbb|  PDB=3pbb  |  SCENE=  }}
-===Crystal structure of human secretory glutaminyl cyclase in complex with PBD150===
+From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
+</div>
+== References ==
-<!--
+<references/>
-The line below this paragraph, {{ABSTRACT_PUBMED_21288892}}, adds the Publication Abstract to the page
+__TOC__
-(as it appears on PubMed at http://www.pubmed.gov), where 21288892 is the PubMed ID number.
+</StructureSection>
--->
-{{ABSTRACT_PUBMED_21288892}}
-==About this Structure==
-[[3pbb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PBB OCA].
-==Reference==
-<ref group="xtra">PMID:021288892</ref><references group="xtra"/>
 [[Category: Glutaminyl-peptide cyclotransferase]]
 [[Category: Homo sapiens]]