9GTE | pdb_00009gte

Crystal structure of TRIM21 PRY-SPRY domain bound to Suramin

PDB DOI: https://doi.org/10.2210/pdb9GTE/pdb

Classification: LIGASE
Organism(s): Mus musculus
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2024-09-17 Released: 2024-10-30
Deposition Author(s): Kim, Y., Knapp, S., Kraemer, A., Structural Genomics Consortium (SGC)
Funding Organization(s): Innovative Medicines Initiative

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.30 Å
R-Value Free:
0.179 (Depositor), 0.191 (DCC)
R-Value Work:
0.159 (Depositor), 0.168 (DCC)
R-Value Observed:
0.160 (Depositor)

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

LOPAC library screening identifies suramin as a TRIM21 binder with a unique binding mode revealed by crystal structure.

Kim, Y., Knapp, S., Kramer, A.

(2025) Acta Crystallogr F Struct Biol Commun 81: 101-107

PubMed: 39955622 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1107/S2053230X25000913
Primary Citation of Related Structures:
9GTE

PubMed Abstract:
Differential scanning fluorimetry screening of the Library of Pharmacologically Active Compounds (LOPAC) identified four hits for the PRYSPRY domain of the human E3 ligase tripartite motif-containing protein 21 (TRIM21). Isothermal titration calorimetry subsequently confirmed suramin as a binder with micromolar affinity. To further investigate the binding mechanism, mouse TRIM21 was used as a structural surrogate due to its improved protein stability and high sequence similarity to the human counterpart. A crystal structure of the complex refined at 1.3 Å resolution revealed a unique binding mode, providing new avenues for targeting TRIM21 and for the development of proteolysis-targeting chimeras (PROTACs).

Organizational Affiliation

Department of Pharmacy, Goethe University Frankfurt, Max-von-Laue Strasse 9, Frankfurt am Main, 60438 Hessen, Germany.

Macromolecule Content

Total Structure Weight: 23.27 kDa
Atom Count: 1,796
Modelled Residue Count: 185
Deposited Residue Count: 188
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
E3 ubiquitin-protein ligase TRIM21	A [auth B]	188	Mus musculus	Mutation(s): 0 Gene Names: Trim21, Ro52, Ssa1 EC: 2.3.2.27
UniProt
Find proteins for Q62191 (Mus musculus) Explore Q62191 Go to UniProtKB: Q62191
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q62191
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SVR (Subject of Investigation/LOI) Query on SVR Download Ideal Coordinates CCD File SDF format, chain H [auth B] MOL2 format, chain H [auth B] mmCIF format, chain H [auth B]	H [auth B]	8,8'-[CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]]BIS-1,3,5-NAPHTHALENETRISULFON IC ACID C₅₁ H₄₀ N₆ O₂₃ S₆ FIAFUQMPZJWCLV-UHFFFAOYSA-N		Interactions Focus chain H [auth B] Interactions & Density Focus chain H [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain B SDF format, chain C [auth B] SDF format, chain D [auth B] SDF format, chain E [auth B] SDF format, chain F [auth B] SDF format, chain G [auth B] MOL2 format, chain B MOL2 format, chain C [auth B] MOL2 format, chain D [auth B] MOL2 format, chain E [auth B] MOL2 format, chain F [auth B] MOL2 format, chain G [auth B] mmCIF format, chain B mmCIF format, chain C [auth B] mmCIF format, chain D [auth B] mmCIF format, chain E [auth B] mmCIF format, chain F [auth B] mmCIF format, chain G [auth B]	B C [auth B] D [auth B] E [auth B] F [auth B] B, C [auth B], D [auth B], E [auth B], F [auth B], G [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain B Focus chain C [auth B] Focus chain D [auth B] Focus chain E [auth B] Focus chain F [auth B] Focus chain G [auth B] Interactions & Density Focus chain B Focus chain C [auth B] Focus chain D [auth B] Focus chain E [auth B] Focus chain F [auth B] Focus chain G [auth B]