7CNO

Phomopsin A in complex with tubulin

PDB DOI: https://doi.org/10.2210/pdb7CNO/pdb

Classification: CELL CYCLE
Organism(s): Sus scrofa, Mus musculus, Gallus gallus
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2020-08-02 Released: 2021-08-04
Deposition Author(s): Wu, C.Y., Wang, Y.X.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.50 ?
R-Value Free: 0.239
R-Value Work: 0.187
R-Value Observed: 0.190

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

The high-resolution X-ray structure of vinca-domain inhibitors of microtubules provides a rational approach for drug design.

Chengyong, W., Jinghong, X., Yanyan, W., Qing-Jie, X., Lingling, M., Yuyan, L., Hai, C., Qian, L., Quan, Z., Bo, S., Yuxi, W.

(2021) FEBS Lett 595: 195-205

PubMed: 33220079 Search on PubMed
DOI: https://doi.org/10.1002/1873-3468.14003
Primary Citation of Related Structures:
7CNM, 7CNN, 7CNO

PubMed Abstract:
Tubulin vinca-domain ligands can inhibit microtubule polymerization, causing cell death in mitosis, and their potential against multiple cancer types has been demonstrated. However, due to drug resistance and toxicities, development of novel vinca-domain ligands is still needed. In this study, we determined the high-resolution crystal structures of vinorelbine, YXD, and Phomopsin A in complex with tubulin at 2.5??. Additionally, we recapitulated all previously published high-resolution crystal structures of the vinca binding site to reveal critical residues and the molecular mechanism of vinca-domain ligands interacting with tubulin. Furthermore, we designed putatively novel triazolopyrimidine derivatives by introducing secondary amine groups to establish salt-bridge and H-bond interactions with Asp179 ^β1 and Asn329 ^α2 . Our studies provided the structural basis for designing novel tubulin vinca-domain ligands.

Organizational Affiliation

Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Macromolecule Content

Total Structure Weight: 266.33 kDa
Atom Count: 18,166
Modelled Residue Count: 2,187
Deposited Residue Count: 2,319
Unique protein chains: 4

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Tubulin alpha-1B chain	A, C	451	Sus scrofa	Mutation(s): 0 EC: 3.6.5
UniProt
Find proteins for Q2XVP4 (Sus scrofa) Explore Q2XVP4 Go to UniProtKB: Q2XVP4
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q2XVP4
Sequence Annotations Expand
Reference Sequence

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Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Tubulin beta chain	B, D	445	Sus scrofa	Mutation(s): 0
UniProt
Find proteins for P02554 (Sus scrofa) Explore P02554 Go to UniProtKB: P02554
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P02554
Sequence Annotations Expand
Reference Sequence

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Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
Stathmin-4	E	143	Mus musculus	Mutation(s): 0 Gene Names: Stmn4
UniProt & NIH Common Fund Data Resources
Find proteins for P63042 (Mus musculus) Explore P63042 Go to UniProtKB: P63042
IMPC: MGI:1931224
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P63042
Sequence Annotations Expand
Reference Sequence

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(by identity cutoff) | 3D Structure

Entity ID: 4
Molecule	Chains	Sequence Length	Organism	Details	Image
Tubulin tyrosine ligase	F [auth G]	384	Gallus gallus	Mutation(s): 0 Gene Names: TTL
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 8 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
HOS Query on HOS Download Ideal Coordinates CCD File SDF format, chain Q [auth B] SDF format, chain V [auth D] MOL2 format, chain Q [auth B] MOL2 format, chain V [auth D] mmCIF format, chain Q [auth B] mmCIF format, chain V [auth D]	Q [auth B], V [auth D]	Phomopsin A C₃₆ H₄₅ Cl N₆ O₁₂ FAFRRYBYQKPKSY-AJSRVUJESA-N		Interactions Focus chain Q [auth B] Focus chain V [auth D] Interactions & Density Focus chain Q [auth B] Focus chain V [auth D]
GTP Query on GTP Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain R [auth C] MOL2 format, chain G [auth A] MOL2 format, chain R [auth C] mmCIF format, chain G [auth A] mmCIF format, chain R [auth C]	G [auth A], R [auth C]	GUANOSINE-5'-TRIPHOSPHATE C₁₀ H₁₆ N₅ O₁₄ P₃ XKMLYUALXHKNFT-UUOKFMHZSA-N		Interactions Focus chain G [auth A] Focus chain R [auth C] Interactions & Density Focus chain G [auth A] Focus chain R [auth C]
ACP Query on ACP Download Ideal Coordinates CCD File SDF format, chain X [auth G] MOL2 format, chain X [auth G] mmCIF format, chain X [auth G]	X [auth G]	PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER C₁₁ H₁₈ N₅ O₁₂ P₃ UFZTZBNSLXELAL-IOSLPCCCSA-N		Interactions Focus chain X [auth G] Interactions & Density Focus chain X [auth G]
GDP Query on GDP Download Ideal Coordinates CCD File SDF format, chain K [auth B] SDF format, chain U [auth D] MOL2 format, chain K [auth B] MOL2 format, chain U [auth D] mmCIF format, chain K [auth B] mmCIF format, chain U [auth D]	K [auth B], U [auth D]	GUANOSINE-5'-DIPHOSPHATE C₁₀ H₁₅ N₅ O₁₁ P₂ QGWNDRXFNXRZMB-UUOKFMHZSA-N		Interactions Focus chain K [auth B] Focus chain U [auth D] Interactions & Density Focus chain K [auth B] Focus chain U [auth D]
MES Query on MES Download Ideal Coordinates CCD File SDF format, chain N [auth B] SDF format, chain O [auth B] MOL2 format, chain N [auth B] MOL2 format, chain O [auth B] mmCIF format, chain N [auth B] mmCIF format, chain O [auth B]	N [auth B], O [auth B]	2-(N-MORPHOLINO)-ETHANESULFONIC ACID C₆ H₁₃ N O₄ S SXGZJKUKBWWHRA-UHFFFAOYSA-N		Interactions Focus chain N [auth B] Focus chain O [auth B] Interactions & Density Focus chain N [auth B] Focus chain O [auth B]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain M [auth B] SDF format, chain T [auth C] SDF format, chain W [auth E] MOL2 format, chain I [auth A] MOL2 format, chain M [auth B] MOL2 format, chain T [auth C] MOL2 format, chain W [auth E] mmCIF format, chain I [auth A] mmCIF format, chain M [auth B] mmCIF format, chain T [auth C] mmCIF format, chain W [auth E]	I [auth A], M [auth B], T [auth C], W [auth E]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain I [auth A] Focus chain M [auth B] Focus chain T [auth C] Focus chain W [auth E] Interactions & Density Focus chain I [auth A] Focus chain M [auth B] Focus chain T [auth C] Focus chain W [auth E]
CL Query on CL 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]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain J [auth A] Interactions & Density Focus chain J [auth A]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain L [auth B] SDF format, chain P [auth B] SDF format, chain S [auth C] MOL2 format, chain H [auth A] MOL2 format, chain L [auth B] MOL2 format, chain P [auth B] MOL2 format, chain S [auth C] mmCIF format, chain H [auth A] mmCIF format, chain L [auth B] mmCIF format, chain P [auth B] mmCIF format, chain S [auth C]	H [auth A], L [auth B], P [auth B], S [auth C]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Focus chain L [auth B] Focus chain P [auth B] Focus chain S [auth C] Interactions & Density Focus chain H [auth A] Focus chain L [auth B] Focus chain P [auth B] Focus chain S [auth C]