2J90

Crystal structure of human ZIP kinase in complex with a tetracyclic pyridone inhibitor (Pyridone 6)

PDB DOI: https://doi.org/10.2210/pdb2J90/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2006-10-31 Released: 2006-11-07
Deposition Author(s): Turnbull, A.P., Berridge, G., Fedorov, O., Pike, A.C.W., Savitsky, P., Eswaran, J., Papagrigoriou, E., Ugochukwa, E., von Delft, F., Gileadi, O., Arrowsmith, C.H., Edwards, A., Weigelt, J., Sundstrom, M., Knapp, S.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.222
R-Value Work: 0.185
R-Value Observed: 0.187

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Activation Segment Dimerization: A Mechanism for Kinase Autophosphorylation of Non-Consensus Sites.

Pike, A.C.W., Rellos, P., Niesen, F.H., Turnbull, A., Oliver, A.W., Parker, S.A., Turk, B.E., Pearl, L.H., Knapp, S.

(2008) EMBO J 27: 704

PubMed: 18239682 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/emboj.2008.8
Primary Citation of Related Structures:
2J51, 2J7T, 2J90, 2JFL, 2JFM, 2UV2

PubMed Abstract:
Protein kinase autophosphorylation of activation segment residues is a common regulatory mechanism in phosphorylation-dependent signalling cascades. However, the molecular mechanisms that guarantee specific and efficient phosphorylation of these sites have not been elucidated. Here, we report on three novel and diverse protein kinase structures that reveal an exchanged activation segment conformation. This dimeric arrangement results in an active kinase conformation in trans, with activation segment phosphorylation sites in close proximity to the active site of the interacting protomer. Analytical ultracentrifugation and chemical cross-linking confirmed the presence of dimers in solution. Consensus substrate sequences for each kinase showed that the identified activation segment autophosphorylation sites are non-consensus substrate sites. Based on the presented structural and functional data, a model for specific activation segment phosphorylation at non-consensus substrate sites is proposed that is likely to be common to other kinases from diverse subfamilies.

Organizational Affiliation

Structural Genomics Consortium, Botnar Research Centre, University of Oxford, Oxford, UK.

Macromolecule Content

Total Structure Weight: 71.32 kDa
Atom Count: 4,633
Modelled Residue Count: 529
Deposited Residue Count: 608
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
DEATH-ASSOCIATED PROTEIN KINASE 3	A, B	304	Homo sapiens	Mutation(s): 0 EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for O43293 (Homo sapiens) Explore O43293 Go to UniProtKB: O43293
PHAROS: O43293 GTEx: ENSG00000167657
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O43293
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
IZA Query on IZA Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain F [auth B] MOL2 format, chain C [auth A] MOL2 format, chain F [auth B]	C [auth A], F [auth B]	2-TERT-BUTYL-9-FLUORO-3,6-DIHYDRO-7H-BENZ[H]-IMIDAZ[4,5-F]ISOQUINOLINE-7-ONE C₁₈ H₁₆ F N₃ O VNDWQCSOSCCWIP-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain F [auth B] Interactions & Density Focus chain C [auth A] Focus chain F [auth B]
PO4 Query on PO4 Download Ideal Coordinates CCD File SDF format, chain J [auth B] MOL2 format, chain J [auth B]	J [auth B]	PHOSPHATE ION O₄ P NBIIXXVUZAFLBC-UHFFFAOYSA-K		Interactions Focus chain J [auth B] Interactions & Density Focus chain J [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain H [auth B] SDF format, chain I [auth B] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B]	E [auth A], H [auth B], I [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain H [auth B] Focus chain I [auth B] Interactions & Density Focus chain E [auth A] Focus chain H [auth B] Focus chain I [auth B]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain G [auth B] MOL2 format, chain D [auth A] MOL2 format, chain G [auth B]	D [auth A], G [auth B]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain D [auth A] Focus chain G [auth B] Interactions & Density Focus chain D [auth A] Focus chain G [auth B]

Modified Residues 2 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
SEP Query on SEP	A, B	L-PEPTIDE LINKING	C₃ H₈ N O₆ P		SER
TPO Query on TPO	A, B	L-PEPTIDE LINKING	C₄ H₁₀ N O₆ P		THR

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.222
R-Value Work: 0.185
R-Value Observed: 0.187
Space Group: P 4₃ 2₁ 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 95.765	α = 90
b = 95.765	β = 90
c = 150.941	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
DENZO	data reduction
SCALEPACK	data scaling
PHASER	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2006-11-07

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2006-11-07
Type: Initial release
Version 1.1: 2011-07-13
Changes: Advisory, Version format compliance
Version 1.2: 2023-12-13
Changes: Data collection, Database references, Derived calculations, Other, Refinement description