1YK8 | pdb_00001yk8

Cathepsin K complexed with a cyanamide-based inhibitor

PDB DOI: https://doi.org/10.2210/pdb1YK8/pdb

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

Deposited: 2005-01-17 Released: 2005-07-19
Deposition Author(s): Barrett, D.G., Deaton, D.N., Hassell, A.M., McFadyen, R.B., Miller, A.B., Miller, L.R., Payne, J.A., Shewchuk, L.M., Willard, D.H., Wright, L.L.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free:
0.277 (Depositor), 0.270 (DCC)
R-Value Work:
0.219 (Depositor), 0.230 (DCC)

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.4 of the entry. See complete history.

Literature

Acyclic cyanamide-based inhibitors of cathepsin K.

Barrett, D.G., Deaton, D.N., Hassell, A.M., McFadyen, R.B., Miller, A.B., Miller, L.R., Payne, J.A., Shewchuk, L.M., Willard, D.H., Wright, L.L.

(2005) Bioorg Med Chem Lett 15: 3039-3043

PubMed: 15896958 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2005.04.032
Primary Citation of Related Structures:
1YK8

PubMed Abstract:
Conversion of the proline-derived cyanamide lead to an acyclic cyanamide capable of forming an additional hydrogen bond with cathepsin K resulted in a large increase in inhibitory activity. An X-ray structure of a co-crystal of a cyanamide with cathepsin K confirmed the enzyme interaction. Furthermore, a representative acyclic cyanamide inhibitor 6r was able to attenuate bone resorption in the rat calvarial model.

Organizational Affiliation

Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.

Macromolecule Content

Total Structure Weight: 23.69 kDa
Atom Count: 1,659
Modelled Residue Count: 213
Deposited Residue Count: 215
Unique protein chains: 1

Macromolecules

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(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 LOADING

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
T2M Query on T2M Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	TERT-BUTYL 2-CYANO-2-METHYLHYDRAZINECARBOXYLATE C₇ H₁₃ N₃ O₂ SWELYBAPJHIOQT-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.277 (Depositor), 0.270 (DCC)
R-Value Work: 0.219 (Depositor), 0.230 (DCC)

Space Group: P 4₃ 2₁ 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 56.383	α = 90
b = 56.383	β = 90
c = 128.431	γ = 90

Software Package:

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

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2005-07-19

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2005-07-19
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
Version 1.4: 2024-11-06
Changes: Structure summary