2wf0: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2wf0]] 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=2WF0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WF0 FirstGlance]. <br> | <table><tr><td colspan='2'>[[2wf0]] 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=2WF0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WF0 FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZY0:N-[(1S,2R)-1-BENZYL-2-HYDROXY-3-{[3-(TRIFLUOROMETHYL)BENZYL]AMINO}PROPYL]-4-ETHYL-8-(2-OXOPYRROLIDIN-1-YL)QUINOLINE-6-CARBOXAMIDE'>ZY0</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZY0:N-[(1S,2R)-1-BENZYL-2-HYDROXY-3-{[3-(TRIFLUOROMETHYL)BENZYL]AMINO}PROPYL]-4-ETHYL-8-(2-OXOPYRROLIDIN-1-YL)QUINOLINE-6-CARBOXAMIDE'>ZY0</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tqf|1tqf]], [[1xn3|1xn3]], [[2vnm|2vnm]], [[1m4h|1m4h]], [[1xn2|1xn2]], [[2fdp|2fdp]], [[2viy|2viy]], [[2vie|2vie]], [[2va6|2va6]], [[2vj6|2vj6]], [[2viz|2viz]], [[2b8l|2b8l]], [[1ym4|1ym4]], [[1sgz|1sgz]], [[2va5|2va5]], [[1ujk|1ujk]], [[2b8v|2b8v]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2va7|2va7]], [[1ym2|1ym2]], [[2vj9|2vj9]], [[2vkm|2vkm]], [[2vnn|2vnn]], [[1py1|1py1]], [[1w50|1w50]], [[1ujj|1ujj]], [[2vj7|2vj7]], [[1w51|1w51]], [[2wf3|2wf3]], [[2wf1|2wf1]], [[2wf4|2wf4]], [[2wez|2wez]], [[2wf2|2wf2]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tqf|1tqf]], [[1xn3|1xn3]], [[2vnm|2vnm]], [[1m4h|1m4h]], [[1xn2|1xn2]], [[2fdp|2fdp]], [[2viy|2viy]], [[2vie|2vie]], [[2va6|2va6]], [[2vj6|2vj6]], [[2viz|2viz]], [[2b8l|2b8l]], [[1ym4|1ym4]], [[1sgz|1sgz]], [[2va5|2va5]], [[1ujk|1ujk]], [[2b8v|2b8v]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2va7|2va7]], [[1ym2|1ym2]], [[2vj9|2vj9]], [[2vkm|2vkm]], [[2vnn|2vnn]], [[1py1|1py1]], [[1w50|1w50]], [[1ujj|1ujj]], [[2vj7|2vj7]], [[1w51|1w51]], [[2wf3|2wf3]], [[2wf1|2wf1]], [[2wf4|2wf4]], [[2wez|2wez]], [[2wf2|2wf2]]</td></tr> | ||
<tr><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='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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2wf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wf0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wf0 RCSB], [http://www.ebi.ac.uk/pdbsum/2wf0 PDBsum]</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=2wf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wf0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wf0 RCSB], [http://www.ebi.ac.uk/pdbsum/2wf0 PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Function == | |||
[[http://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> | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
[[Category: Brien, A O | [[Category: Brien, A O]] | ||
[[Category: Charrier, N | [[Category: Charrier, N]] | ||
[[Category: Clarke, B | [[Category: Clarke, B]] | ||
[[Category: Cutler, L | [[Category: Cutler, L]] | ||
[[Category: Demont, E | [[Category: Demont, E]] | ||
[[Category: Dingwall, C | [[Category: Dingwall, C]] | ||
[[Category: Dunsdon, R | [[Category: Dunsdon, R]] | ||
[[Category: Hawkins, J | [[Category: Hawkins, J]] | ||
[[Category: Howes, C | [[Category: Howes, C]] | ||
[[Category: Hubbard, J | [[Category: Hubbard, J]] | ||
[[Category: Hussain, I | [[Category: Hussain, I]] | ||
[[Category: Maile, G | [[Category: Maile, G]] | ||
[[Category: Matico, R | [[Category: Matico, R]] | ||
[[Category: Mosley, J | [[Category: Mosley, J]] | ||
[[Category: Naylor, A | [[Category: Naylor, A]] | ||
[[Category: Redshaw, S | [[Category: Redshaw, S]] | ||
[[Category: Rowland, P | [[Category: Rowland, P]] | ||
[[Category: Smith, K J | [[Category: Smith, K J]] | ||
[[Category: Soleil, V | [[Category: Soleil, V]] | ||
[[Category: Sweitzer, S | [[Category: Sweitzer, S]] | ||
[[Category: Theobald, P | [[Category: Theobald, P]] | ||
[[Category: Vesey, D | [[Category: Vesey, D]] | ||
[[Category: Walter, D S | [[Category: Walter, D S]] | ||
[[Category: Wayne, G | [[Category: Wayne, G]] | ||
[[Category: Asp-2]] | [[Category: Asp-2]] | ||
[[Category: Aspartyl protease]] | [[Category: Aspartyl protease]] | ||
Revision as of 23:52, 25 December 2014
HUMAN BACE-1 IN COMPLEX WITH 4-ETHYL-N-((1S,2R)-2-HYDROXY-1-(PHENYLMETHYL)-3-(((3-(TRIFLUOROMETHYL)PHENYL)METHYL)AMINO) PROPYL)-8-(2-OXO-1-PYRROLIDINYL)-6-QUINOLINECARBOXAMIDEHUMAN BACE-1 IN COMPLEX WITH 4-ETHYL-N-((1S,2R)-2-HYDROXY-1-(PHENYLMETHYL)-3-(((3-(TRIFLUOROMETHYL)PHENYL)METHYL)AMINO) PROPYL)-8-(2-OXO-1-PYRROLIDINYL)-6-QUINOLINECARBOXAMIDE
Structural highlights
Function[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.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedInhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. We have recently disclosed a series of transition-state mimetic BACE-1 inhibitors showing nanomolar potency in cell-based assays. Amongst them, GSK188909 (compound 2) had favorable pharmacokinetics and was the first orally bioavailable inhibitor reported to demonstrate brain amyloid lowering in an animal model. In this Letter, we describe the reasons that led us to favor a second generation of inhibitors for further in vivo studies. Second generation of BACE-1 inhibitors. Part 1: The need for improved pharmacokinetics.,Charrier N, Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, Hawkins J, Howes C, Hubbard J, Hussain I, Maile G, Matico R, Mosley J, Naylor A, O'Brien A, Redshaw S, Rowland P, Soleil V, Smith KJ, Sweitzer S, Theobald P, Vesey D, Walter DS, Wayne G Bioorg Med Chem Lett. 2009 Jul 1;19(13):3664-8. Epub 2009 Apr 17. PMID:19428244[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCACategories:
- Homo sapiens
- Memapsin 2
- Brien, A O
- Charrier, N
- Clarke, B
- Cutler, L
- Demont, E
- Dingwall, C
- Dunsdon, R
- Hawkins, J
- Howes, C
- Hubbard, J
- Hussain, I
- Maile, G
- Matico, R
- Mosley, J
- Naylor, A
- Redshaw, S
- Rowland, P
- Smith, K J
- Soleil, V
- Sweitzer, S
- Theobald, P
- Vesey, D
- Walter, D S
- Wayne, G
- Asp-2
- Aspartyl protease
- Bace-1
- Beta-secretase
- Beta-site app cleaving enzyme
- Disulfide bond
- Glycoprotein
- Hydrolase
- Memapsin-2
- Membrane
- Protease
- Transmembrane
- Zymogen