2vij | pdb_00002vij
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
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| 2vij, resolution 1.60Å | |||||||||||||
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| Sites: | AC1 and AC2 | ||||||||||||
| Ligands: | C44 | ||||||||||||
| Activity: | Memapsin 2, with EC number 3.4.23.46 | ||||||||||||
| Related: | 1M4H, 1SGZ, 1W50, 1W51, 1XS7, 1YM4, 1FKN, 1PY1, 1TQF, 1UJJ, 1UJK, 1XN2, 1XN3, 1YM2, 2B8L, 2B8V, 2VA5, 2VA6, 2VA7, 2VIE
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
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. 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. 2008 Feb 1;18(3):1022-6. Epub 2007 Dec 15. PMID:18171615
Page seeded by OCA on Mon Mar 31 05:12:42 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Homo sapiens
- Memapsin 2
- Single protein
- Beswick, P.
- Brien, A O.
- Charrier, N.
- Clarke, B.
- Demont, E.
- Dingwall, C.
- Dunsdon, R.
- Faller, A.
- Gleave, R.
- Hawkins, J.
- Hussain, I.
- Johnson, C.
- Macpherson, D.
- Maile, G.
- Matico, R.
- Milner, P.
- Mosley, J.
- Naylor, A.
- Redshaw, S.
- Riddell, D.
- Rowland, P.
- Skidmore, J.
- Smith, K.
- Soleil, V.
- Stanway, S.
- Stemp, G.
- Stuart, A.
- Sweitzer, S.
- Theobald, P.
- Vesey, D.
- Walter, D S.
- Ward, J.
- Wayne, G.
- Alternative splicing
- Asp-2
- Aspartyl protease
- Bace-1
- Beta-secretase
- Beta-site app cleaving enzyme
- Glycoprotein
- Hydrolase
- Memapsin-2
- Membrane
- Protease
- Transmembrane
- Zymogen
