5v0n: Difference between revisions
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==BACE1 in complex with inhibitor 5g== | |||
<StructureSection load='5v0n' size='340' side='right'caption='[[5v0n]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5v0n]] is a 3 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=5V0N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V0N FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.155Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8W4:N-{(1S,2S)-1-[(2S)-4-BENZYL-3-OXOPIPERAZIN-2-YL]-1-HYDROXY-3-PHENYLPROPAN-2-YL}-7-ETHYL-1,3,3-TRIMETHYL-2,2-DIOXO-1,2,3,4-TETRAHYDRO-2LAMBDA~6~-[1,2,5]THIADIAZEPINO[3,4,5-HI]INDOLE-9-CARBOXAMIDE'>8W4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=URE:UREA'>URE</scene></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=5v0n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v0n OCA], [https://pdbe.org/5v0n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v0n RCSB], [https://www.ebi.ac.uk/pdbsum/5v0n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v0n 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 == | |||
We report the design and synthesis of a series of BACE1 inhibitors incorporating mono- and bicyclic 6-substituted 2-oxopiperazines as novel P1' and P2' ligands and isophthalamide derivative as P2-P3 ligands. Among mono-substituted 2-oxopiperazines, inhibitor 5a with N-benzyl-2-oxopiperazine and isophthalamide showed potent BACE1 inhibitory activity (Ki=2nM). Inhibitor 5g, with N-benzyl-2-oxopiperazine and substituted indole-derived P2-ligand showed a reduction in potency. The X-ray crystal structure of 5g-bound BACE1 was determined and used to design a set of disubstituted 2-oxopiperazines and bicyclic derivatives that were subsequently investigated. Inhibitor 6j with an oxazolidinone derivative showed a BACE1 inhibitory activity of 23nM and cellular EC50 of 80nM. | |||
Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1'-P2' ligands.,Ghosh AK, Brindisi M, Yen YC, Cardenas EL, Ella-Menye JR, Kumaragurubaran N, Huang X, Tang J, Mesecar AD Bioorg Med Chem Lett. 2017 Apr 8. pii: S0960-894X(17)30369-4. doi:, 10.1016/j.bmcl.2017.04.011. PMID:28427814<ref>PMID:28427814</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5v0n" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta secretase 3D structures|Beta secretase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Ghosh A]] | |||
[[Category: Mesecar A]] | |||
[[Category: Yen Y-C]] | |||
Latest revision as of 13:38, 4 October 2023
BACE1 in complex with inhibitor 5g
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