4AU8

Crystal structure of compound 4a in complex with cdk5, showing an unusual binding mode to the hinge region via a water molecule

PDB DOI: https://doi.org/10.2210/pdb4AU8/pdb

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

Deposited: 2012-05-14 Released: 2013-03-27
Deposition Author(s): Malmstrom, J., Viklund, J., Slivo, C., Costa, A., Maudet, M., Sandelin, C., Hiller, G., Olsson, L.L., Aagaard, A., Geschwindner, S., Xue, Y., Vasange, M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.90 Å
R-Value Free: 0.234
R-Value Work: 0.196
R-Value Observed: 0.197

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.0 of the entry. See complete history.

Literature

Synthesis and Structure-Activity Relationship of 4-(1,3-Benzothiazol-2-Yl)-Thiophene-2-Sulfonamides as Cyclin-Dependent Kinase 5 (Cdk5)/P25 Inhibitors.

Malmstrom, J., Viklund, J., Slivo, C., Costa, A., Maudet, M., Sandelin, C., Hiller, G., Olsson, L.L., Aagaard, A., Geschwindner, S., Xue, Y., Vasange, M.

(2012) Bioorg Med Chem Lett 22: 5919

PubMed: 22889803 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2012.07.068
Primary Citation of Related Structures:
4AU8

PubMed Abstract:
4-(1,3-Benzothiazol-2-yl)thiophene-2-sulfonamide (4a) was found to be a moderately potent inhibitor of cyclin-dependent kinase 5 (cdk5) from a HTS screen. The synthesis and SAR around this hit is described. The X-ray coordinates of ligand 4a with cdk5 are also reported, showing an unusual binding mode to the hinge region via a water molecule.

Organizational Affiliation

Medicinal Chemistry, CNSP iMed Science, AstraZeneca R&D, Innovative Medicines, SE-15185 Södertälje, Sweden. Jonas.Malmstrom@astrazeneca.com

Macromolecule Content

Total Structure Weight: 68.48 kDa
Atom Count: 4,994
Modelled Residue Count: 553
Deposited Residue Count: 592
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
CYCLIN-DEPENDENT KINASE 5	A, B	296	Homo sapiens	Mutation(s): 0 EC: 2.7.11.22
UniProt & NIH Common Fund Data Resources
Find proteins for Q00535 (Homo sapiens) Explore Q00535 Go to UniProtKB: Q00535
PHAROS: Q00535 GTEx: ENSG00000164885
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q00535
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
Z3R Query on Z3R Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain J [auth B] MOL2 format, chain F [auth A] MOL2 format, chain J [auth B]	F [auth A], J [auth B]	4-(1,3-benzothiazol-2-yl)thiophene-2-sulfonamide C₁₁ H₈ N₂ O₂ S₃ GKGZVFYMXSXLJJ-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain J [auth B] Interactions & Density Focus chain F [auth A] Focus chain J [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain G [auth B] SDF format, chain H [auth B] SDF format, chain I [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain G [auth B] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B]	C [auth A] D [auth A] E [auth A] G [auth B] H [auth B] C [auth A], D [auth A], E [auth A], G [auth B], H [auth B], I [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain G [auth B] Focus chain H [auth B] Focus chain I [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain G [auth B] Focus chain H [auth B] Focus chain I [auth B]
IMD Query on IMD Download Ideal Coordinates CCD File SDF format, chain K [auth B] MOL2 format, chain K [auth B]	K [auth B]	IMIDAZOLE C₃ H₅ N₂ RAXXELZNTBOGNW-UHFFFAOYSA-O		Interactions Focus chain K [auth B] Interactions & Density Focus chain K [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
Z3R	Binding MOAD: 4AU8	IC50: 551 (nM) from 1 assay(s)
	BindingDB: 4AU8	IC50: 551 (nM) from 1 assay(s)
	PDBBind: 4AU8	IC50: 551 (nM) from 1 assay(s)