7ZTL

Crystal structure of a covalently linked Aurora-A N-Myc complex

PDB DOI: https://doi.org/10.2210/pdb7ZTL/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2022-05-11 Released: 2023-01-18
Deposition Author(s): Diebold, M., Schindelin, H.
Funding Organization(s): German Research Foundation (DFG)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.90 Å
R-Value Free: 0.193
R-Value Work: 0.163
R-Value Observed: 0.165

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Crystal structure of a covalently linked Aurora-A-MYCN complex.

Diebold, M., Schonemann, L., Eilers, M., Sotriffer, C., Schindelin, H.

(2023) Acta Crystallogr D Struct Biol 79: 1-9

PubMed: 36601802 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1107/S2059798322011433
Primary Citation of Related Structures:
7ZTL

PubMed Abstract:
Formation of the Aurora-A-MYCN complex increases levels of the oncogenic transcription factor MYCN in neuroblastoma cells by abrogating its degradation through the ubiquitin proteasome system. While some small-molecule inhibitors of Aurora-A were shown to destabilize MYCN, clinical trials have not been satisfactory to date. MYCN itself is considered to be `undruggable' due to its large intrinsically disordered regions. Targeting the Aurora-A-MYCN complex rather than Aurora-A or MYCN alone will open new possibilities for drug development and screening campaigns. To overcome the challenges that a ternary system composed of Aurora-A, MYCN and a small molecule entails, a covalently cross-linked construct of the Aurora-A-MYCN complex was designed, expressed and characterized, thus enabling screening and design campaigns to identify selective binders.

Organizational Affiliation

Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.

Macromolecule Content

Total Structure Weight: 44.18 kDa
Atom Count: 2,589
Modelled Residue Count: 282
Deposited Residue Count: 371
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Aurora kinase A	A	309	Homo sapiens	Mutation(s): 3 Gene Names: AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for O14965 (Homo sapiens) Explore O14965 Go to UniProtKB: O14965
PHAROS: O14965 GTEx: ENSG00000087586
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O14965
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
N-myc proto-oncogene protein	B	62	Homo sapiens	Mutation(s): 1
UniProt & NIH Common Fund Data Resources
Find proteins for P04198 (Homo sapiens) Explore P04198 Go to UniProtKB: P04198
PHAROS: P04198 GTEx: ENSG00000134323
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P04198
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 6 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
ADP Query on ADP Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A] mmCIF format, chain C [auth A]	C [auth A]	ADENOSINE-5'-DIPHOSPHATE C₁₀ H₁₅ N₅ O₁₀ P₂ XTWYTFMLZFPYCI-KQYNXXCUSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
JWG (Subject of Investigation/LOI) Query on JWG Download Ideal Coordinates CCD File SDF format, chain K [auth B] MOL2 format, chain K [auth B] mmCIF format, chain K [auth B]	K [auth B]	4-(3-hydroxy-3-oxopropylamino)-4-oxidanylidene-butanoic acid C₇ H₁₁ N O₅ NFQWOKKYYQQDCQ-UHFFFAOYSA-N		Interactions Focus chain K [auth B] Interactions & Density Focus chain K [auth B]
BCN Query on BCN Download Ideal Coordinates CCD File SDF format, chain H [auth A] MOL2 format, chain H [auth A] mmCIF format, chain H [auth A]	H [auth A]	BICINE C₆ H₁₃ N O₄ FSVCELGFZIQNCK-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Interactions & Density Focus chain H [auth A]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain I [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain I [auth A] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain I [auth A]	F [auth A], G [auth A], I [auth A]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain G [auth A] Focus chain I [auth A] Interactions & Density Focus chain F [auth A] Focus chain G [auth A] Focus chain I [auth A]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A]	D [auth A], E [auth A]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Interactions & Density Focus chain D [auth A] Focus chain E [auth A]
NA Query on NA Download Ideal Coordinates CCD File SDF format, chain J [auth A] MOL2 format, chain J [auth A] mmCIF format, chain J [auth A]	J [auth A]	SODIUM ION Na FKNQFGJONOIPTF-UHFFFAOYSA-N		Interactions Focus chain J [auth A] Interactions & Density Focus chain J [auth A]