2vij

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Revision as of 09:01, 31 January 2008

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spinqualitylabelsall models 2vij, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

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 Structure

2VIJ is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Memapsin 2, with EC number 3.4.23.46 Known structural/functional Sites: and . Full crystallographic information is available from 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. 2007 Dec 15;. PMID:18171615

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