3udh: Difference between revisions

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-[[Image:3udh.jpg|left|200px]]
-<!--
+==Crystal Structure of BACE with Compound 1==
-The line below this paragraph, containing "STRUCTURE_3udh", creates the "Structure Box" on the page.
+<StructureSection load='3udh' size='340' side='right'caption='[[3udh]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3udh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UDH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UDH FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=091:(3S)-SPIRO[INDOLE-3,3-PYRROLIDIN]-2(1H)-ONE'>091</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_3udh|  PDB=3udh  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3udh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3udh OCA], [https://pdbe.org/3udh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3udh RCSB], [https://www.ebi.ac.uk/pdbsum/3udh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3udh ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/BACE1_HUMAN BACE1_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.<ref>PMID:10677483</ref> <ref>PMID:20354142</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The aspartyl protease beta-secretase, or BACE1, has been demonstrated to be a key factor in the proteolytic formation of Abeta-peptide, a major component of plaques in the brains of Alzheimer's Disease (AD) patients, and inhibition of this enzyme has emerged as a major strategy for pharmacologic intervention in AD. An X-ray based fragment screen of Pfizer's proprietary fragment collection has resulted in the identification of a novel BACE binder featuring spiropyrrolidine framework. Although exhibiting only weak inhibitory activity against the BACE enzyme, the small compound was verified by biophysical and NMR-based methods as a bona fide BACE inhibitor. Subsequent optimization of the lead compound, relying heavily on structure-based drug design and computational prediction of physiochemical properties, resulted in a 1000-fold improvement in potency while maintaining ligand efficiency and properties predictive of good permeability and low P-gp liability.
-===Crystal Structure of BACE with Compound 1===
+Discovery and Optimization of a Novel Spiro-pyrrolidine Inhibitors of beta-Secretase (BACE1) Through Fragment Based Drug Design.,Efremov IV, Vajdos FF, Borzilleri K, Capetta S, Dorff PH, Dutra JK, Mansour M, Chen H, Goldstein SW, Noell S, Oborski CE, O'Connell TN, O'Sullivan TJ, Pandit J, Wang H, Wei B, Withka JM, McColl A J Med Chem. 2012 Apr 2. PMID:22468999<ref>PMID:22468999</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3udh" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22468999}}, adds the Publication Abstract to the page
+*[[Beta secretase 3D structures|Beta secretase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 22468999 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22468999}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[3udh]] is a 1 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=3UDH OCA].
-==Reference==
-<ref group="xtra">PMID:022468999</ref><ref group="xtra">PMID:018289105</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Memapsin 2]]
+[[Category: Large Structures]]
-[[Category: Borzilleri, K.]]
+[[Category: Borzilleri K]]
-[[Category: Capetta, S.]]
+[[Category: Capetta S]]
-[[Category: Connell, T O.]]
+[[Category: Dorff P]]
-[[Category: Dorff, P.]]
+[[Category: Dutra J]]
-[[Category: Dutra, J.]]
+[[Category: Efremov IV]]
-[[Category: Efremov, I V.]]
+[[Category: Mansour M]]
-[[Category: Mansour, M.]]
+[[Category: O'Connell T]]
-[[Category: Oborski, C.]]
+[[Category: O'Sullivan TJ]]
-[[Category: Pandit, J.]]
+[[Category: Oborski C]]
-[[Category: Sullivan, T J.O.]]
+[[Category: Pandit J]]
-[[Category: Vajdos, F F.]]
+[[Category: Vajdos FF]]
-[[Category: Wang, H.]]
+[[Category: Wang H]]
-[[Category: Withka, J.]]
+[[Category: Withka J]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]