PDBsum entry 3nsh

Hydrolase

PDB id: 3nsh

Contents

Protein chains

372 a.a. *

Ligands

957 ×3

Waters ×356

* Residue conservation analysis

PDB id:

3nsh

Name:

Hydrolase

Title:

Bace-1 in complex with eln475957

Structure:

Beta-secretase 1. Chain: a, b, c. Synonym: beta-site amyloid precursor protein cleaving enzyme 1, beta- site app cleaving enzyme 1, membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, asp 2, asp2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: bace1, bace, kiaa1149. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.20Å R-factor: 0.233 R-free: 0.279

Authors:

G.D.Probst,S.Bowers,J.M.Sealy,E.Brecht,N.Yao

Key ref:

G.D.Probst et al. (2010). Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: structure-activity relationship of the aryl region. Bioorg Med Chem Lett, 20, 6034-6039. PubMed id: 20822903

Date:

01-Jul-10 Release date: 22-Sep-10

Protein chains

P56817  (BACE1_HUMAN) -  Beta-secretase 1 from Homo sapiens

Seq: 501 a.a.

Struc: 372 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.23.46 - memapsin 2.

Bioorg Med Chem Lett 20:6034-6039 (2010)

PubMed id: 20822903

Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: structure-activity relationship of the aryl region.

G.D.Probst, S.Bowers, J.M.Sealy, B.Stupi, D.Dressen, B.M.Jagodzinska, J.Aquino, A.Gailunas, A.P.Truong, L.Tso, Y.Z.Xu, R.K.Hom, V.John, J.S.Tung, M.A.Pleiss, J.A.Tucker, A.W.Konradi, H.L.Sham, J.Jagodzinski, G.Toth, E.Brecht, N.Yao, H.Pan, M.Lin, D.R.Artis, L.Ruslim, M.P.Bova, S.Sinha, T.A.Yednock, S.Gauby, W.Zmolek, K.P.Quinn, J.M.Sauer.

ABSTRACT

The structure-activity relationship of the prime region of hydroxyethylamine BACE inhibitors is described. Variation in the aryl linker region with 5- and 6-membered heterocycles provided compounds such as 33 with improved permeability and reduced P-gp liability compared to benzyl amine analog 1.