1XS7

Crystal Structure of a cycloamide-urethane-derived novel inhibitor bound to human brain memapsin 2 (beta-secretase).


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase).

Ghosh, A.K.Devasamudram, T.Hong, L.Dezutter, C.Xu, X.Weerasena, V.Koelsch, G.Bilcer, G.Tang, J.

(2005) Bioorg Med Chem Lett 15: 15-20

  • DOI: https://doi.org/10.1016/j.bmcl.2004.10.084
  • Primary Citation of Related Structures:  
    1XS7

  • PubMed Abstract: 

    A series of novel macrocyclic amide-urethanes was designed and synthesized based upon the X-ray crystal structure of our lead inhibitor (1, OM99-2 with eight residues) bound to memapsin 2. Ring size and substituent effects have been investigated. Cycloamide-urethanes containing 14- to 16-membered rings exhibited low nanomolar inhibitory potencies against human brain memapsin 2 (beta-secretase).


  • Organizational Affiliation

    Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA. arunghos@uic.edu


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1A [auth D]389Homo sapiensMutation(s): 0 
Gene Names: BACE1BACE
EC: 3.4.23.46
UniProt & NIH Common Fund Data Resources
Find proteins for P56817 (Homo sapiens)
Explore P56817 
Go to UniProtKB:  P56817
PHAROS:  P56817
GTEx:  ENSG00000186318 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP56817
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MMI
Query on MMI

Download Ideal Coordinates CCD File 
B [auth D]N-[(4S,5S,7R)-8-({(S)-1-[(BENZYLAMINO)OXOMETHYL]-2-METHYLPROPYL}AMINO)-5-HYDROXY-2,7-DIMETHYL-8-OXO-OCT-4-YL]-(4S,7S)-4 -ISOPROPYL-2,5,9-TRIOXO-1-OXA-3,6,10-TRIAZACYCLOHEXADECANE-7-CARBOXAMIDE
C38 H62 N6 O8
QJAPFAZHNSZLJE-CWURXVSKSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
MMI BindingDB:  1XS7 Ki: min: 25, max: 25.1 (nM) from 2 assay(s)
PDBBind:  1XS7 Ki: 25.1 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 85.839α = 90
b = 87.807β = 89.81
c = 130.644γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-12-21
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary