2HM1

Crystal Structure of human beta-secretase (BACE) in the presence of an inhibitor (2)

PDB DOI: https://doi.org/10.2210/pdb2HM1/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2006-07-10 Released: 2007-01-23
Deposition Author(s): Benson, T.E., Prince, D.B., Tomasselli, A.G., Emmons, T.L., Paddock, D.J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.20 Å
R-Value Free: 0.251
R-Value Work: 0.204

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Design of potent inhibitors of human beta-secretase. Part 2.

Freskos, J.N., Fobian, Y.M., Benson, T.E., Moon, J.B., Bienkowski, M.J., Brown, D.L., Emmons, T.L., Heintz, R., Laborde, A., McDonald, J.J., Mischke, B.V., Molyneaux, J.M., Mullins, P.B., Bryan Prince, D., Paddock, D.J., Tomasselli, A.G., Winterrowd, G.

(2007) Bioorg Med Chem Lett 17: 78-81

PubMed: 17049233 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2006.09.091
Primary Citation of Related Structures:
2HM1

PubMed Abstract:
We describe an optimized series of acyclic hydroxyethylamine transition state isosteres of beta-secretase that incorporates a variety of P(2) side chains that yield potent inhibitors with excellent cellular activity. A 2.2A crystal structure of compound 13 is shown.

Organizational Affiliation

Pfizer Inc., 700N. Chesterfield Pkwy., St. Louis, MO 63198, USA.

Macromolecule Content

Total Structure Weight: 46.09 kDa
Atom Count: 3,165
Modelled Residue Count: 375
Deposited Residue Count: 406
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Beta-secretase 1	A	406	Homo sapiens	Mutation(s): 0 Gene Names: BACE 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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P56817
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
LIQ Query on LIQ Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	N-{(1S)-2-({(1S,2R)-1-(3,5-DIFLUOROBENZYL)-3-[(3-ETHYLBENZYL)AMINO]-2-HYDROXYPROPYL}AMINO)-2-OXO-1-[(PENTYLSULFONYL)METHYL]ETHYL}NICOTINAMIDE C₃₃ H₄₂ F₂ N₄ O₅ S IOTPZWJUHSYLHJ-OJDZSJEKSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
LIQ	PDBBind: 2HM1	IC50: 2 (nM) from 1 assay(s)
LIQ	Binding MOAD: 2HM1	IC50: 2 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.20 Å
R-Value Free: 0.251
R-Value Work: 0.204
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 72.99	α = 90
b = 104.88	β = 94.99
c = 50.06	γ = 90

Software Package:

Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
CNS	refinement
PDB_EXTRACT	data extraction

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2007-01-23

Deposition Author(s):

Tomasselli, A.G.

Revision History (Full details and data files)

Version 1.0: 2007-01-23
Type: Initial release
Version 1.1: 2008-05-01
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 1.3: 2017-10-18
Changes: Refinement description

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.