4gid
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4gid]] is a 4 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=4GID OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GID FirstGlance]. <br> | <table><tr><td colspan='2'>[[4gid]] is a 4 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=4GID OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GID FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0GH:N-[(2S)-1-({(2S,3R)-3-HYDROXY-1-[(2-METHYLPROPYL)AMINO]-1-OXOBUTAN-2-YL}AMINO)-3-PHENYLPROPAN-2-YL]-5-[METHYL(METHYLSULFONYL)AMINO]-N-[(1R)-1-PHENYLETHYL]BENZENE-1,3-DICARBOXAMIDE'>0GH</scene>, <scene name='pdbligand=LPD:L-PROLINAMIDE'>LPD</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]] 2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0GH:N-[(2S)-1-({(2S,3R)-3-HYDROXY-1-[(2-METHYLPROPYL)AMINO]-1-OXOBUTAN-2-YL}AMINO)-3-PHENYLPROPAN-2-YL]-5-[METHYL(METHYLSULFONYL)AMINO]-N-[(1R)-1-PHENYLETHYL]BENZENE-1,3-DICARBOXAMIDE'>0GH</scene>, <scene name='pdbligand=LPD:L-PROLINAMIDE'>LPD</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=4gid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gid OCA], [https://pdbe.org/4gid PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gid RCSB], [https://www.ebi.ac.uk/pdbsum/4gid PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gid ProSAT]</span></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=4gid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gid OCA], [https://pdbe.org/4gid PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gid RCSB], [https://www.ebi.ac.uk/pdbsum/4gid PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gid ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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> | [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 structure-based design, synthesis, and X-ray structure of protein-ligand complexes of exceptionally potent and selective beta-secretase inhibitors are described. The inhibitors are designed specifically to interact with S(1)' active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 5 has exhibited exceedingly potent inhibitory activity (K(i) = 17 pM) and high selectivity over BACE 2 (>7000-fold) and cathepsin D (>250000-fold). A protein-ligand crystal structure revealed important molecular insight into these selectivities. These interactions may serve as an important guide to design selectivity over the physiologically important aspartic acid proteases. | ||
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| - | Structure-Based Design of Highly Selective beta-Secretase Inhibitors: Synthesis, Biological Evaluation, and Protein-Ligand X-ray Crystal Structure.,Ghosh AK, Venkateswara Rao K, Yadav ND, Anderson DD, Gavande N, Huang X, Terzyan S, Tang J J Med Chem. 2012 Sep 6. PMID:22954357<ref>PMID:22954357</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4gid" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Revision as of 15:47, 14 March 2024
Structure of beta-secretase complexed with inhibitor
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Categories: Homo sapiens | Large Structures | Anderson D | Gavande N | Ghosh A | Huang X | Tang J | Terzyan S | Venkateswara RK | Yadav N
