2R6N

Crystal structure of a pyrrolopyrimidine inhibitor in complex with human Cathepsin K

PDB DOI: https://doi.org/10.2210/pdb2R6N/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): No

Deposited: 2007-09-06 Released: 2007-11-06
Deposition Author(s): Cowan-Jacob, S.W., Ramage, P., Mathis, B., Geisse, S.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.95 Å
R-Value Free: 0.184
R-Value Work: 0.156

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Novel scaffold for cathepsin K inhibitors.

Teno, N., Miyake, T., Ehara, T., Irie, O., Sakaki, J., Ohmori, O., Gunji, H., Matsuura, N., Masuya, K., Hitomi, Y., Nonomura, K., Horiuchi, M., Gohda, K., Iwasaki, A., Umemura, I., Tada, S., Kometani, M., Iwasaki, G., Cowan-Jacob, S.W., Missbach, M., Lattmann, R., Betschart, C.

(2007) Bioorg Med Chem Lett 17: 6096-6100

PubMed: 17911019 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2007.09.047
Primary Citation of Related Structures:
2R6N

PubMed Abstract:
Pyrrolopyrimidine, a novel scaffold, allows to adjust interactions within the S3 subsite of cathepsin K. The core intermediate 10 facilitated the P3 optimization and identified highly potent and selective cathepsin K inhibitors 11-20.

Organizational Affiliation

Novartis Institutes for BioMedical Research, Ohkubo 8, Tsukuba, Ibaraki, Japan. naoki.teno@novartis.com

Macromolecule Content

Total Structure Weight: 24.16 kDa
Atom Count: 1,906
Modelled Residue Count: 216
Deposited Residue Count: 217
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Cathepsin K	A	217	Homo sapiens	Mutation(s): 0 Gene Names: CTSK, CTSO, CTSO2 EC: 3.4.22.38
UniProt & NIH Common Fund Data Resources
Find proteins for P43235 (Homo sapiens) Explore P43235 Go to UniProtKB: P43235
PHAROS: P43235 GTEx: ENSG00000143387
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P43235
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
CKE Query on CKE Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	1-{7-cyclohexyl-6-[4-(4-methylpiperazin-1-yl)benzyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl}methanamine C₂₅ H₃₄ N₆ GCJSOJRPNOWSEH-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
CKE	PDBBind: 2R6N	IC50: 1 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.95 Å
R-Value Free: 0.184
R-Value Work: 0.156
Space Group: P 6₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 62.4	α = 90
b = 62.4	β = 90
c = 121.8	γ = 120

Software Package:

Software Name	Purpose
AMoRE	phasing
CNS	refinement
PDB_EXTRACT	data extraction
MAR345dtb	data collection
XDS	data reduction
AUTOMAR	data reduction

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2007-11-06

Deposition Author(s):

Cowan-Jacob, S.W.

Revision History (Full details and data files)

Version 1.0: 2007-11-06
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance
Version 1.2: 2017-10-25
Changes: Advisory, 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.