6YDZ

Human wtSTING in complex with 3',3'-cGAMP

PDB DOI: https://doi.org/10.2210/pdb6YDZ/pdb

Classification: PROTEIN BINDING
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21
Mutation(s): No

Deposited: 2020-03-23 Released: 2021-03-31
Deposition Author(s): Boura, E., Smola, M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.90 ?
R-Value Free: 0.252
R-Value Work: 0.218
R-Value Observed: 0.219

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

Ligand Strain and Its Conformational Complexity Is a Major Factor in the Binding of Cyclic Dinucleotides to STING Protein.

Smola, M., Gutten, O., Dejmek, M., Kozisek, M., Evangelidis, T., Tehrani, Z.A., Novotna, B., Nencka, R., Birkus, G., Rulisek, L., Boura, E.

(2021) Angew Chem Int Ed Engl 60: 10172-10178

PubMed: 33616279 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1002/anie.202016805
Primary Citation of Related Structures:
6Y99, 6YDB, 6YDZ, 6YEA, 6Z0Z, 6Z15

PubMed Abstract:
STING (stimulator of interferon genes) is a key regulator of innate immunity that has recently been recognized as a promising drug target. STING is activated by cyclic dinucleotides (CDNs) which eventually leads to expression of type I interferons and other cytokines. Factors underlying the affinity of various CDN analogues are poorly understood. Herein, we correlate structural biology, isothermal calorimetry (ITC) and computational modeling to elucidate factors contributing to binding of six CDNs-three pairs of natural (ribo) and fluorinated (2'-fluororibo) 3',3'-CDNs. X-ray structural analyses of six {STING:CDN} complexes did not offer any explanation for the different affinities of the studied ligands. ITC showed entropy/enthalpy compensation up to 25?kcal?mol ^-1 for this set of similar ligands. The higher affinities of fluorinated analogues are explained with help of computational methods by smaller loss of entropy upon binding and by smaller strain (free) energy.

Organizational Affiliation

Gilead Sciences Research Centre at IOCB, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 2, 16610, Prague, Czech Republic.

Macromolecule Content

Total Structure Weight: 23.86 kDa
Atom Count: 1,422
Modelled Residue Count: 176
Deposited Residue Count: 204
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Stimulator of interferon protein	A	204	Homo sapiens	Mutation(s): 0 Gene Names: STING, LOC340061, hCG_1782396
UniProt & NIH Common Fund Data Resources
Find proteins for Q86WV6 (Homo sapiens) Explore Q86WV6 Go to UniProtKB: Q86WV6
PHAROS: Q86WV6 GTEx: ENSG00000184584
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q86WV6
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
4BW (Subject of Investigation/LOI) Query on 4BW Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	2-amino-9-[(2R,3R,3aS,5R,7aR,9R,10R,10aS,12R,14aR)-9-(6-amino-9H-purin-9-yl)-3,5,10,12-tetrahydroxy-5,12-dioxidooctahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecin-2-yl]-1,9-dihydro-6H-purin-6-one C₂₀ H₂₄ N₁₀ O₁₃ P₂ RFCBNSCSPXMEBK-INFSMZHSSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]