6GT3

Crystal Structure of the A2A-StaR2-bRIL562 in complex with AZD4635 at 2.0A resolution

PDB DOI: https://doi.org/10.2210/pdb6GT3/pdb

Classification: MEMBRANE PROTEIN
Organism(s): Homo sapiens, Escherichia coli
Expression System: Trichoplusia ni
Mutation(s): Yes
Membrane Protein: Yes PDBTMMemProtMD

Deposited: 2018-06-15 Released: 2019-06-26
Deposition Author(s): Borodovsky, A., Wang, Y., Deng, N., Ye, M., Stephen, T.L., Goodwin, K., Goodwin, R., Strittmatter, N., Shaw, J., Sachsenmeier, K., Clarke, J.D., Hay, C., Reimer, C., Andrews, S.P., Brown, G.A., Congreve, M., Cheng, R.K.Y., Dore, A.S., Mason, J.S., Marshall, F.H., Weir, M.P., Lyne, P., Woessner, R.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.201
R-Value Work: 0.183
R-Value Observed: 0.183

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

Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity

Borodovsky, A., Barbon, C.M., Wang, Y., Ye, M., Prickett, L., Chandra, D., Shaw, J., Deng, N., Sachsenmeier, K., Clarke, J.D., Linghu, B., Brown, G.A., Brown, J., Congreve, M., Cheng, R.K.Y., Dore, A.S., Hurrell, E., Shao, W., Woessner, R., Reimer, C., Drew, L., Fawell, S., Schuller, A.G., Mele, D.A.

(2020) J Immunother Cancer

Macromolecule Content

Total Structure Weight: 57.3 kDa
Atom Count: 3,812
Modelled Residue Count: 388
Deposited Residue Count: 433
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Adenosine receptor A2a,Soluble cytochrome b562,Adenosine receptor A2a	A	433	Homo sapiens, Escherichia coli	Mutation(s): 11 Gene Names: ADORA2A, ADORA2, cybC Membrane Entity: Yes
UniProt & NIH Common Fund Data Resources
Find proteins for P0ABE7 (Escherichia coli) Explore P0ABE7 Go to UniProtKB: P0ABE7
Find proteins for P29274 (Homo sapiens) Explore P29274 Go to UniProtKB: P29274
PHAROS: P29274 GTEx: ENSG00000128271
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Groups	P0ABE7P29274
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
CLR Query on CLR Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A]	D [auth A], E [auth A], F [auth A]	CHOLESTEROL C₂₇ H₄₆ O HVYWMOMLDIMFJA-DPAQBDIFSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A]
OLC Query on OLC Download Ideal Coordinates CCD File SDF format, chain AA [auth A] SDF format, chain BA [auth A] SDF format, chain CA [auth A] SDF format, chain DA [auth A] SDF format, chain EA [auth A] SDF format, chain V [auth A] SDF format, chain W [auth A] SDF format, chain X [auth A] SDF format, chain Y [auth A] SDF format, chain Z [auth A] MOL2 format, chain AA [auth A] MOL2 format, chain BA [auth A] MOL2 format, chain CA [auth A] MOL2 format, chain DA [auth A] MOL2 format, chain EA [auth A] MOL2 format, chain V [auth A] MOL2 format, chain W [auth A] MOL2 format, chain X [auth A] MOL2 format, chain Y [auth A] MOL2 format, chain Z [auth A] mmCIF format, chain AA [auth A] mmCIF format, chain BA [auth A] mmCIF format, chain CA [auth A] mmCIF format, chain DA [auth A] mmCIF format, chain EA [auth A] mmCIF format, chain V [auth A] mmCIF format, chain W [auth A] mmCIF format, chain X [auth A] mmCIF format, chain Y [auth A] mmCIF format, chain Z [auth A]	AA [auth A] BA [auth A] CA [auth A] DA [auth A] EA [auth A] AA [auth A], BA [auth A], CA [auth A], DA [auth A], EA [auth A], V [auth A], W [auth A], X [auth A], Y [auth A], Z [auth A]	(2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate C₂₁ H₄₀ O₄ RZRNAYUHWVFMIP-GDCKJWNLSA-N		Interactions Focus chain AA [auth A] Focus chain BA [auth A] Focus chain CA [auth A] Focus chain DA [auth A] Focus chain EA [auth A] Focus chain V [auth A] Focus chain W [auth A] Focus chain X [auth A] Focus chain Y [auth A] Focus chain Z [auth A] Interactions & Density Focus chain AA [auth A] Focus chain BA [auth A] Focus chain CA [auth A] Focus chain DA [auth A] Focus chain EA [auth A] Focus chain V [auth A] Focus chain W [auth A] Focus chain X [auth A] Focus chain Y [auth A] Focus chain Z [auth A]
F9Q (Subject of Investigation/LOI) Query on F9Q 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]	6-(2-chloranyl-6-methyl-pyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine C₁₅ H₁₁ Cl F N₅ NCWQLHHDGDXIJN-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
OLA Query on OLA Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain L [auth A] SDF format, chain M [auth A] SDF format, chain N [auth A] SDF format, chain O [auth A] SDF format, chain P [auth A] SDF format, chain Q [auth A] SDF format, chain R [auth A] SDF format, chain S [auth A] SDF format, chain T [auth A] SDF format, chain U [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain L [auth A] MOL2 format, chain M [auth A] MOL2 format, chain N [auth A] MOL2 format, chain O [auth A] MOL2 format, chain P [auth A] MOL2 format, chain Q [auth A] MOL2 format, chain R [auth A] MOL2 format, chain S [auth A] MOL2 format, chain T [auth A] MOL2 format, chain U [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain L [auth A] mmCIF format, chain M [auth A] mmCIF format, chain N [auth A] mmCIF format, chain O [auth A] mmCIF format, chain P [auth A] mmCIF format, chain Q [auth A] mmCIF format, chain R [auth A] mmCIF format, chain S [auth A] mmCIF format, chain T [auth A] mmCIF format, chain U [auth A]	G [auth A] H [auth A] I [auth A] J [auth A] K [auth A] G [auth A], H [auth A], I [auth A], J [auth A], K [auth A], L [auth A], M [auth A], N [auth A], O [auth A], P [auth A], Q [auth A], R [auth A], S [auth A], T [auth A], U [auth A]	OLEIC ACID C₁₈ H₃₄ O₂ ZQPPMHVWECSIRJ-KTKRTIGZSA-N		Interactions Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain P [auth A] Focus chain Q [auth A] Focus chain R [auth A] Focus chain S [auth A] Focus chain T [auth A] Focus chain U [auth A] Interactions & Density Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain P [auth A] Focus chain Q [auth A] Focus chain R [auth A] Focus chain S [auth A] Focus chain T [auth A] Focus chain U [auth A]
NA Query on NA 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]	SODIUM ION Na FKNQFGJONOIPTF-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
F9Q	BindingDB: 6GT3	Ki: min: 1.7, max: 13.8 (nM) from 2 assay(s)
		IC50: 299 (nM) from 1 assay(s)
		EC50: 725 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.201
R-Value Work: 0.183
R-Value Observed: 0.183
Space Group: C 2 2 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 39.55	α = 90
b = 179.714	β = 90
c = 140.776	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
XDS	data reduction
Aimless	data scaling
PHASER	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2019-06-26

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2019-06-26
Type: Initial release
Version 1.1: 2020-07-08
Changes: Database references
Version 1.2: 2024-01-17
Changes: Data collection, Database references, Derived calculations, Refinement description
Version 1.3: 2024-10-23
Changes: Structure summary