2ypu
From Proteopedia
(Difference between revisions)
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<StructureSection load='2ypu' size='340' side='right' caption='[[2ypu]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='2ypu' size='340' side='right' caption='[[2ypu]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | [[2ypu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2yb3 2yb3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YPU OCA]. <br> | + | <table><tr><td colspan='2'>[[2ypu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2yb3 2yb3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YPU OCA]. <br> |
| - | <b>[[Ligand|Ligands:]]</b> <scene name='pdbligand=I41:2-[[2-[[(2S)-3-(3H-IMIDAZOL-4-YL)-1-METHOXY-1-OXO-PROPAN-2-YL]AMINO]-2-OXO-ETHYL]-(PHENYLMETHYL)AMINO]ETHANOIC+ACID'>I41</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> | + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I41:2-[[2-[[(2S)-3-(3H-IMIDAZOL-4-YL)-1-METHOXY-1-OXO-PROPAN-2-YL]AMINO]-2-OXO-ETHYL]-(PHENYLMETHYL)AMINO]ETHANOIC+ACID'>I41</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> |
| - | <b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span>< | + | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr> |
| - | <b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ypu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ypu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ypu RCSB], [http://www.ebi.ac.uk/pdbsum/2ypu PDBsum]</span>< | + | <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=2ypu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ypu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ypu RCSB], [http://www.ebi.ac.uk/pdbsum/2ypu PDBsum]</span></td></tr> |
| + | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Insulin degrading enzyme (IDE) is a highly conserved zinc metalloprotease that is involved in the clearance of various physiologically peptides like amyloid-beta and insulin. This enzyme has been involved in the physiopathology of diabetes and Alzheimer's disease. We describe here a series of small molecules discovered by screening. Co-crystallization of the compounds with IDE revealed a binding both at the permanent exosite and at the discontinuous, conformational catalytic site. Preliminary structure-activity relationships are described. Selective inhibition of amyloid-beta degradation over insulin hydrolysis was possible. Neuroblastoma cells treated with the optimized compound display a dose-dependent increase in amyloid-beta levels. | Insulin degrading enzyme (IDE) is a highly conserved zinc metalloprotease that is involved in the clearance of various physiologically peptides like amyloid-beta and insulin. This enzyme has been involved in the physiopathology of diabetes and Alzheimer's disease. We describe here a series of small molecules discovered by screening. Co-crystallization of the compounds with IDE revealed a binding both at the permanent exosite and at the discontinuous, conformational catalytic site. Preliminary structure-activity relationships are described. Selective inhibition of amyloid-beta degradation over insulin hydrolysis was possible. Neuroblastoma cells treated with the optimized compound display a dose-dependent increase in amyloid-beta levels. | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 09:33, 1 May 2014
human insulin degrading enzyme E111Q in complex with inhibitor compound 41367
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