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2vj9

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Revision as of 20:38, 19 September 2018

Human BACE-1 in complex with N-((1S,2R)-3-(cyclohexylamino)-2-hydroxy- 1-(phenylmethyl)propyl)-3-(ethylamino)-5-(2-oxo-1-pyrrolidinyl) benzamide

Structural highlights

2vj9 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1tqf, 1xn3, 1m4h, 1xn2, 2viy, 2vie, 2va6, 2vj6, 2viz, 2b8l, 1ym4, 2va5, 1sgz, 2b8v, 1ujk, 1fkn, 1xs7, 2vij, 2va7, 1ym2, 2vkm, 1py1, 1w50, 2vj7, 1ujj, 1w51
Activity:	Memapsin 2, with EC number 3.4.23.46
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P(1)(') and P(2)(') substituents, two different binding modes were observed in X-ray co-crystal structures.

BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character.,Clarke B, Demont E, Dingwall C, Dunsdon R, Faller A, Hawkins J, Hussain I, MacPherson D, Maile G, Matico R, Milner P, Mosley J, Naylor A, O'Brien A, Redshaw S, Riddell D, Rowland P, Soleil V, Smith KJ, Stanway S, Stemp G, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G Bioorg Med Chem Lett. 2008 Feb 1;18(3):1017-21. Epub 2007 Dec 15. PMID:18166458^[3]

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

References

↑ Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J. Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1456-60. PMID:10677483
↑ Okada H, Zhang W, Peterhoff C, Hwang JC, Nixon RA, Ryu SH, Kim TW. Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing. FASEB J. 2010 Aug;24(8):2783-94. doi: 10.1096/fj.09-146357. Epub 2010 Mar 30. PMID:20354142 doi:10.1096/fj.09-146357
↑ Clarke B, Demont E, Dingwall C, Dunsdon R, Faller A, Hawkins J, Hussain I, MacPherson D, Maile G, Matico R, Milner P, Mosley J, Naylor A, O'Brien A, Redshaw S, Riddell D, Rowland P, Soleil V, Smith KJ, Stanway S, Stemp G, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G. BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character. Bioorg Med Chem Lett. 2008 Feb 1;18(3):1017-21. Epub 2007 Dec 15. PMID:18166458 doi:10.1016/j.bmcl.2007.12.019

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2vj9"

@@ Line 1: / Line 1: @@
-==HUMAN BACE-1 IN COMPLEX WITH N-((1S,2R)-3-(CYCLOHEXYLAMINO)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)-3-(ETHYLAMINO)-5-(2-OXO-1-PYRROLIDINYL)BENZAMIDE==
+==Human BACE-1 in complex with N-((1S,2R)-3-(cyclohexylamino)-2-hydroxy- 1-(phenylmethyl)propyl)-3-(ethylamino)-5-(2-oxo-1-pyrrolidinyl) benzamide==
 <StructureSection load='2vj9' size='340' side='right' caption='[[2vj9]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tqf|1tqf]], [[1xn3|1xn3]], [[1m4h|1m4h]], [[1xn2|1xn2]], [[2viy|2viy]], [[2vie|2vie]], [[2va6|2va6]], [[2vj6|2vj6]], [[2viz|2viz]], [[2b8l|2b8l]], [[1ym4|1ym4]], [[2va5|2va5]], [[1sgz|1sgz]], [[2b8v|2b8v]], [[1ujk|1ujk]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2va7|2va7]], [[1ym2|1ym2]], [[2vkm|2vkm]], [[1py1|1py1]], [[1w50|1w50]], [[2vj7|2vj7]], [[1ujj|1ujj]], [[1w51|1w51]]</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=2vj9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vj9 OCA], [http://pdbe.org/2vj9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vj9 RCSB], [http://www.ebi.ac.uk/pdbsum/2vj9 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=2vj9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vj9 OCA], [http://pdbe.org/2vj9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vj9 RCSB], [http://www.ebi.ac.uk/pdbsum/2vj9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vj9 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vj/2vj9_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vj/2vj9_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 46: / Line 47: @@
 [[Category: Hawkins, J]]
 [[Category: Hussain, I]]
-[[Category: Macpherson, D]]
+[[Category: MacPherson, D]]
 [[Category: Maile, G]]
 [[Category: Matico, R]]
@@ Line 65: / Line 66: @@
 [[Category: Ward, J]]
 [[Category: Wayne, G]]
+[[Category: Alternative splicing]]
 [[Category: Asp-2]]
 [[Category: Aspartyl protease]]

2vj9

From Proteopedia

Revision as of 20:38, 19 September 2018

Human BACE-1 in complex with N-((1S,2R)-3-(cyclohexylamino)-2-hydroxy- 1-(phenylmethyl)propyl)-3-(ethylamino)-5-(2-oxo-1-pyrrolidinyl) benzamide

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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