4dpf: Difference between revisions

Line 1:

[[~~Image~~:~~4dpf~~.~~png~~|~~left~~|~~200px~~]]

==BACE-1 in complex with a HEA-macrocyclic type inhibitor==

== Structural highlights ==

<table><tr><td colspan='2'>[[4dpf]] 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=4DPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DPF FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0LG:N-[(4S,8E,11S)-4-[(1R)-1-HYDROXY-2-{[3-(PROPAN-2-YL)BENZYL]AMINO}ETHYL]-2,13-DIOXO-11-PHENYL-6-OXA-3,12-DIAZABICYCLO[12.3.1]OCTADECA-1(18),8,14,16-TETRAEN-16-YL]-N-METHYLMETHANESULFONAMIDE'>0LG</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dpi|4dpi]]</td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] </span></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dpf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dpf RCSB], [http://www.ebi.ac.uk/pdbsum/4dpf PDBsum]</span></td></tr>

</table>

== Publication Abstract from PubMed ==

A series of P1-P3 linked macrocyclic BACE-1 inhibitors containing a hydroxyethylamine (HEA) isostere scaffold has been synthesized. All inhibitors comprise a toluene or N-phenylmethanesulfonamide P2 moiety. Excellent BACE-1 potencies, both in enzymatic and cell-based assays, were observed in this series of target compounds, with the best candidates displaying cell-based IC(50) values in the low nanomolar range. As an attempt to improve potency, a phenyl substituent aiming at the S3 subpocket was introduced in the macrocyclic ring. X-ray analyzes were performed on selected compounds, and enzyme-inhibitor interactions are discussed.

~~{{STRUCTURE_4dpf| PDB=4dpf | SCENE= }}~~

Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: Design, synthesis and X-ray crystal structures of enzyme inhibitor complexes.,Sandgren V, Agback T, Johansson PO, Lindberg J, Kvarnstrom I, Samuelsson B, Belda O, Dahlgren A Bioorg Med Chem. 2012 Jul 15;20(14):4377-89. Epub 2012 May 24. PMID:22698785<ref>PMID:22698785</ref>

~~===BACE-1 in complex with~~ a ~~HEA-macrocyclic type inhibitor===~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

~~{{ABSTRACT_PUBMED_22698785}}~~

==See Also==

*[[Beta secretase|Beta secretase]]

==~~About this Structure~~==

== References ==

[[~~4dpf]] 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=4DPF OCA~~].

__TOC__

==~~Reference~~==

</StructureSection>

<~~ref group="xtra">PMID:022698785<~~/~~ref~~><~~references group="xtra"~~/>

[[Category: Homo sapiens]]

[[Category: Memapsin 2]]

[[Category: Borkakoti, N.]]

[[Category: Borkakoti, N]]

[[Category: Derbyshire, D.]]

[[Category: Derbyshire, D]]

[[Category: Lindberg, J.]]

[[Category: Lindberg, J]]

[[Category: Asp2]]

[[Category: Bace]]

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@@ Line 1: / Line 1: @@
-[[Image:4dpf.png|left|200px]]
+==BACE-1 in complex with a HEA-macrocyclic type inhibitor==
+<StructureSection load='4dpf' size='340' side='right' caption='[[4dpf]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4dpf]] 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=4DPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DPF FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0LG:N-[(4S,8E,11S)-4-[(1R)-1-HYDROXY-2-{[3-(PROPAN-2-YL)BENZYL]AMINO}ETHYL]-2,13-DIOXO-11-PHENYL-6-OXA-3,12-DIAZABICYCLO[12.3.1]OCTADECA-1(18),8,14,16-TETRAEN-16-YL]-N-METHYLMETHANESULFONAMIDE'>0LG</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dpi|4dpi]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dpf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dpf RCSB], [http://www.ebi.ac.uk/pdbsum/4dpf PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A series of P1-P3 linked macrocyclic BACE-1 inhibitors containing a hydroxyethylamine (HEA) isostere scaffold has been synthesized. All inhibitors comprise a toluene or N-phenylmethanesulfonamide P2 moiety. Excellent BACE-1 potencies, both in enzymatic and cell-based assays, were observed in this series of target compounds, with the best candidates displaying cell-based IC(50) values in the low nanomolar range. As an attempt to improve potency, a phenyl substituent aiming at the S3 subpocket was introduced in the macrocyclic ring. X-ray analyzes were performed on selected compounds, and enzyme-inhibitor interactions are discussed.
-{{STRUCTURE_4dpf|  PDB=4dpf  |  SCENE=  }}
+Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: Design, synthesis and X-ray crystal structures of enzyme inhibitor complexes.,Sandgren V, Agback T, Johansson PO, Lindberg J, Kvarnstrom I, Samuelsson B, Belda O, Dahlgren A Bioorg Med Chem. 2012 Jul 15;20(14):4377-89. Epub 2012 May 24. PMID:22698785<ref>PMID:22698785</ref>
-===BACE-1 in complex with a HEA-macrocyclic type inhibitor===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_22698785}}
+==See Also==
+*[[Beta secretase|Beta secretase]]
-==About this Structure==
+== References ==
-[[4dpf]] 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=4DPF OCA].
+<references/>
+__TOC__
-==Reference==
+</StructureSection>
-<ref group="xtra">PMID:022698785</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
 [[Category: Memapsin 2]]
-[[Category: Borkakoti, N.]]
+[[Category: Borkakoti, N]]
-[[Category: Derbyshire, D.]]
+[[Category: Derbyshire, D]]
-[[Category: Lindberg, J.]]
+[[Category: Lindberg, J]]
 [[Category: Asp2]]
 [[Category: Bace]]