1YK7

Cathepsin K complexed with a cyanopyrrolidine inhibitor

PDB DOI: https://doi.org/10.2210/pdb1YK7/pdb

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

Deposited: 2005-01-17 Released: 2005-03-22
Deposition Author(s): Barrett, D.G., Deaton, D.N., Hassell, A.M., McFadyen, R.B., Miller, A.B., Miller, L.R., Shewchuk, L.M., Tavares, F.X., Willard, D.H., Wright, L.L.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.50 Å
R-Value Free: 0.270
R-Value Work: 0.190

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Novel and potent cyclic cyanamide-based cathepsin K inhibitors.

Deaton, D.N., Hassell, A.M., McFadyen, R.B., Miller, A.B., Miller, L.R., Shewchuk, L.M., Tavares, F.X., Willard, D.H., Wright, L.L.

(2005) Bioorg Med Chem Lett 15: 1815-1819

PubMed: 15780613 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2005.02.033
Primary Citation of Related Structures:
1YK7

PubMed Abstract:
Starting from a PDE IV inhibitor hit derived from high throughput screening of the compound collection, a key pyrrolidine cyanamide pharmacophore was identified. Modifications of the pyrrolidine ring produced enhancements in cathepsin K inhibition. An X-ray co-crystal structure of a cyanamide with cathepsin K confirmed the mode of inhibition.

Organizational Affiliation

Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. david.n.deaton@gsk.com

Macromolecule Content

Total Structure Weight: 23.88 kDa
Atom Count: 1,782
Modelled Residue Count: 215
Deposited Residue Count: 215
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	215	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
NBL Query on NBL Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	N2-[(BENZYLOXY)CARBONYL]-N1-[(3S)-1-CYANOPYRROLIDIN-3-YL]-L-LEUCINAMIDE C₁₉ H₂₆ N₄ O₃ IMTUSTXBVIALBC-SJORKVTESA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
NBL	PDBBind: 1YK7	IC50: 19 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.50 Å
R-Value Free: 0.270
R-Value Work: 0.190
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 32.241	α = 90
b = 66.653	β = 90
c = 93.187	γ = 90

Software Package:

Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
CNS	refinement
CNS	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2005-03-22

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2005-03-22
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