4EB6

Tubulin-Vinblastine: Stathmin-like complex

PDB DOI: https://doi.org/10.2210/pdb4EB6/pdb

Classification: STRUCTURAL PROTEIN/INHIBITOR
Organism(s): Ovis aries, Rattus norvegicus
Expression System: Escherichia coli BL21(DE3)
Mutation(s): Yes

Deposited: 2012-03-23 Released: 2012-08-01
Deposition Author(s): Ranaivoson, F.M., Gigant, B., Knossow, M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.47 Å
R-Value Free: 0.253
R-Value Work: 0.213
R-Value Observed: 0.215

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Structural plasticity of tubulin assembly probed by vinca-domain ligands.

Ranaivoson, F.M., Gigant, B., Berritt, S., Joullie, M., Knossow, M.

(2012) Acta Crystallogr D Biol Crystallogr 68: 927-934

PubMed: 22868758 Search on PubMed
DOI: https://doi.org/10.1107/S0907444912017143
Primary Citation of Related Structures:
3UT5, 4EB6

PubMed Abstract:
Vinca-domain ligands are compounds that bind to tubulin at its inter-heterodimeric interface and favour heterogeneous protofilament-like assemblies, giving rise to helices and rings. This is the basis for their inhibition of microtubule assembly, for their antimitotic activities and for their use in anticancer chemotherapy. Ustiloxins are vinca-domain ligands with a well established total synthesis. A 2.7 Å resolution structure of ustiloxin D bound to the vinca domain embedded in the complex of two tubulins with the stathmin-like domain of RB3 (T(2)R) has been determined. This finding precisely defines the interactions of ustiloxins with tubulin and, taken together with structures of other vinca-ligand complexes, allows structure-based suggestions to be made for improved activity. These comparisons also provide a rationale for the large-scale polymorphism of the protofilament-like assemblies mediated by vinca-domain ligands based on local differences in their interactions with the two tubulin heterodimers constituting their binding site.

Organizational Affiliation

Laboratoire d'Enzymologie et Biochimie Structurales, Centre de Recherche de Gif, CNRS, 91198 Gif-sur-Yvette, France.

Macromolecule Content

Total Structure Weight: 220.49 kDa
Atom Count: 14,918
Modelled Residue Count: 1,861
Deposited Residue Count: 1,934
Unique protein chains: 3

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Tubulin alpha chain	A, C	451	Ovis aries	Mutation(s): 0
UniProt
Find proteins for D0VWZ0 (Ovis aries) Explore D0VWZ0 Go to UniProtKB: D0VWZ0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	D0VWZ0
Sequence Annotations Expand
Reference Sequence

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(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Tubulin beta chain	B, D	445	Ovis aries	Mutation(s): 0
UniProt
Find proteins for D0VWY9 (Ovis aries) Explore D0VWY9 Go to UniProtKB: D0VWY9
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	D0VWY9
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
Stathmin-4	E	142	Rattus norvegicus	Mutation(s): 2 Gene Names: Stmn4
UniProt
Find proteins for P63043 (Rattus norvegicus) Explore P63043 Go to UniProtKB: P63043
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P63043
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
VLB Query on VLB Download Ideal Coordinates CCD File SDF format, chain N [auth C] MOL2 format, chain N [auth C] mmCIF format, chain N [auth C]	N [auth C]	(2ALPHA,2'BETA,3BETA,4ALPHA,5BETA)-VINCALEUKOBLASTINE C₄₆ H₅₈ N₄ O₉ JXLYSJRDGCGARV-CFWMRBGOSA-N		Interactions Focus chain N [auth C] Interactions & Density Focus chain N [auth C]
GTP Query on GTP Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain L [auth C] MOL2 format, chain F [auth A] MOL2 format, chain L [auth C] mmCIF format, chain F [auth A] mmCIF format, chain L [auth C]	F [auth A], L [auth C]	GUANOSINE-5'-TRIPHOSPHATE C₁₀ H₁₆ N₅ O₁₄ P₃ XKMLYUALXHKNFT-UUOKFMHZSA-N		Interactions Focus chain F [auth A] Focus chain L [auth C] Interactions & Density Focus chain F [auth A] Focus chain L [auth C]
GDP Query on GDP Download Ideal Coordinates CCD File SDF format, chain J [auth B] SDF format, chain O [auth D] MOL2 format, chain J [auth B] MOL2 format, chain O [auth D] mmCIF format, chain J [auth B] mmCIF format, chain O [auth D]	J [auth B], O [auth D]	GUANOSINE-5'-DIPHOSPHATE C₁₀ H₁₅ N₅ O₁₁ P₂ QGWNDRXFNXRZMB-UUOKFMHZSA-N		Interactions Focus chain J [auth B] Focus chain O [auth D] Interactions & Density Focus chain J [auth B] Focus chain O [auth D]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain Q [auth D] SDF format, chain I [auth A] SDF format, chain K [auth B] SDF format, chain P [auth D] MOL2 format, chain H [auth A] MOL2 format, chain Q [auth D] MOL2 format, chain I [auth A] MOL2 format, chain K [auth B] MOL2 format, chain P [auth D] mmCIF format, chain H [auth A] mmCIF format, chain Q [auth D] mmCIF format, chain I [auth A] mmCIF format, chain K [auth B] mmCIF format, chain P [auth D]	H [auth A], I [auth A], K [auth B], P [auth D], Q [auth D]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain H [auth A] Focus chain I [auth A] Focus chain K [auth B] Focus chain P [auth D] Focus chain Q [auth D] Interactions & Density Focus chain H [auth A] Focus chain I [auth A] Focus chain K [auth B] Focus chain P [auth D] Focus chain Q [auth D]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain M [auth C] MOL2 format, chain G [auth A] MOL2 format, chain M [auth C] mmCIF format, chain G [auth A] mmCIF format, chain M [auth C]	G [auth A], M [auth C]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain M [auth C] Interactions & Density Focus chain G [auth A] Focus chain M [auth C]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 3.47 Å
R-Value Free: 0.253
R-Value Work: 0.213
R-Value Observed: 0.215
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 64.69	α = 90
b = 129.68	β = 90
c = 252.75	γ = 90

Software Package:

Software Name	Purpose
ADSC	data collection
AMoRE	phasing
BUSTER	refinement
XDS	data reduction
SCALA	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2012-08-01

Deposition Author(s):

Ranaivoson, F.M.

Gigant, B.

Knossow, M.

Revision History (Full details and data files)

Version 1.0: 2012-08-01
Type: Initial release
Version 1.1: 2013-01-23
Changes: Database references
Version 1.2: 2024-02-28
Changes: Data collection, Database references, Derived calculations