1Q6K

Cathepsin K complexed with t-butyl(1S)-1-cyclohexyl-2-oxoethylcarbamate

PDB DOI: https://doi.org/10.2210/pdb1Q6K/pdb

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

Deposited: 2003-08-13 Released: 2004-03-16
Deposition Author(s): Catalano, J.G., Deaton, D.N., Furfine, E.S., Hassell, A.M., McFadyen, R.B., Miller, A.B., Miller, L.R., Shewchuk, L.M., Willard, D.H., Wright, L.L.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Observed: 0.200

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.5 of the entry. See complete history.

Literature

Exploration of the P1 SAR of aldehyde cathepsin K inhibitors

Catalano, J.G., Deaton, D.N., Furfine, E.S., Hassell, A.M., McFadyen, R.B., Miller, A.B., Miller, L.R., Shewchuk, L.M., Willard, D.H., Wright, L.L.

(2004) Bioorg Med Chem Lett 14: 275-278

PubMed: 14684342 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2003.09.088
Primary Citation of Related Structures:
1Q6K

PubMed Abstract:
The synthesis and biological activity of a series of aldehyde inhibitors of cathepsin K are reported. Exploration of the properties of the S(1) subsite with a series of alpha-amino aldehyde derivatives substituted at the P(1) position afforded compounds with cathepsin K IC(50)s between 52 microM and 15 nM.

Organizational Affiliation

Department of Medicinal Chemistry, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA.

Macromolecule Content

Total Structure Weight: 23.86 kDa
Atom Count: 1,813
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 OR CTSO 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 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
TCO Query on TCO Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A]	C [auth A]	TERT-BUTYL(1S)-1-CYCLOHEXYL-2-OXOETHYLCARBAMATE C₁₃ H₂₃ N O₃ BDSGOSWEKUGHOV-LLVKDONJSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
TCO	BindingDB: 1Q6K	IC50: 26 (nM) from 1 assay(s)
	PDBBind: 1Q6K	IC50: 26 (nM) from 1 assay(s)
	Binding MOAD: 1Q6K	IC50: 26 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Observed: 0.200
Space Group: P 4₃ 2₁ 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 56.443	α = 90
b = 56.443	β = 90
c = 130.212	γ = 90

Software Package:

Software Name	Purpose
SCALEPACK	data scaling
X-PLOR	model building
X-PLOR	refinement
X-PLOR	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2004-03-16

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2004-03-16
Type: Initial release
Version 1.1: 2008-04-29
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 1.3: 2017-10-11
Changes: Refinement description
Version 1.4: 2018-02-14
Changes: Experimental preparation
Version 1.5: 2023-08-16
Changes: Data collection, Database references, Derived calculations, Refinement description