2vij: Difference between revisions

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Revision as of 19:46, 20 March 2008

File:2vij.gif

, resolution 1.60Å

Sites:

and

Ligands:

Activity:

Memapsin 2, with EC number 3.4.23.46

Coordinates:

save as pdb, mmCIF, xml

HUMAN BACE-1 IN COMPLEX WITH 3-(1,1-DIOXIDOTETRAHYDRO-2H-1, 2-THIAZIN-2-YL)-5-(ETHYLAMINO)-N-((1S,2R)-2-HYDROXY-1-(PHENYLMETHYL)-3-(1,2,3,4-TETRAHYDRO-1-NAPHTHALENYLAMINO) PROPYL)BENZAMIDE

OverviewOverview

This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays.

About this StructureAbout this Structure

2VIJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

BACE-1 inhibitors part 3: identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells., Beswick P, Charrier N, Clarke B, Demont E, Dingwall C, Dunsdon R, Faller A, Gleave R, Hawkins J, Hussain I, Johnson CN, MacPherson D, Maile G, Matico R, Milner P, Mosley J, Naylor A, O'Brien A, Redshaw S, Riddell D, Rowland P, Skidmore J, Soleil V, Smith KJ, Stanway S, Stemp G, Stuart A, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1022-6. Epub 2007 Dec 15. PMID:18171615

Page seeded by OCA on Thu Mar 20 18:46:55 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2vij.gif|left|200px]]<br /><applet load="2vij" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2vij.gif|left|200px]]
-caption="2vij, resolution 1.60&Aring;" />
-'''HUMAN BACE-1 IN COMPLEX WITH 3-(1,1-DIOXIDOTETRAHYDRO-2H-1, 2-THIAZIN-2-YL)-5-(ETHYLAMINO)-N-((1S,2R)-2-HYDROXY-1-(PHENYLMETHYL)-3-(1,2,3,4-TETRAHYDRO-1-NAPHTHALENYLAMINO) PROPYL)BENZAMIDE'''<br />
+ {{Structure
+|PDB= 2vij |SIZE=350|CAPTION= <scene name='initialview01'>2vij</scene>, resolution 1.60&Aring;
+|SITE= <scene name='pdbsite=AC1:C44+Binding+Site+For+Chain+A'>AC1</scene> and <scene name='pdbsite=AC2:C44+Binding+Site+For+Chain+A'>AC2</scene>
+|LIGAND= <scene name='pdbligand=C44:'>C44</scene>
+|ACTIVITY= [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]
+|GENE=
+}}
+'''HUMAN BACE-1 IN COMPLEX WITH 3-(1,1-DIOXIDOTETRAHYDRO-2H-1, 2-THIAZIN-2-YL)-5-(ETHYLAMINO)-N-((1S,2R)-2-HYDROXY-1-(PHENYLMETHYL)-3-(1,2,3,4-TETRAHYDRO-1-NAPHTHALENYLAMINO) PROPYL)BENZAMIDE'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-VIJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=C44:'>C44</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Known structural/functional Sites: <scene name='pdbsite=AC1:C44+Binding+Site+For+Chain+A'>AC1</scene> and <scene name='pdbsite=AC2:C44+Binding+Site+For+Chain+A'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VIJ OCA].
+VIJ is a [[Single protein]] structure of 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=2VIJ OCA].
 ==Reference==
-BACE-1 inhibitors part 3: identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells., Beswick P, Charrier N, Clarke B, Demont E, Dingwall C, Dunsdon R, Faller A, Gleave R, Hawkins J, Hussain I, Johnson CN, MacPherson D, Maile G, Matico R, Milner P, Mosley J, Naylor A, O'Brien A, Redshaw S, Riddell D, Rowland P, Skidmore J, Soleil V, Smith KJ, Stanway S, Stemp G, Stuart A, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1022-6. Epub 2007 Dec 15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18171615 18171615]
+BACE-1 inhibitors part 3: identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells., Beswick P, Charrier N, Clarke B, Demont E, Dingwall C, Dunsdon R, Faller A, Gleave R, Hawkins J, Hussain I, Johnson CN, MacPherson D, Maile G, Matico R, Milner P, Mosley J, Naylor A, O'Brien A, Redshaw S, Riddell D, Rowland P, Skidmore J, Soleil V, Smith KJ, Stanway S, Stemp G, Stuart A, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1022-6. Epub 2007 Dec 15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18171615 18171615]
 [[Category: Homo sapiens]]
 [[Category: Memapsin 2]]
@@ Line 62: / Line 71: @@
 [[Category: zymogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:56:10 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:46:55 2008''