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- PDB-7aro: Crystal structure of the non-ribose partial agonist LUF5833 bound... -

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Basic information

Entry
Database: PDB / ID: 7aro
TitleCrystal structure of the non-ribose partial agonist LUF5833 bound to the adenosine A2A receptor
ComponentsAdenosine receptor A2a,Soluble cytochrome b562,Adenosine receptor A2a
KeywordsMEMBRANE PROTEIN / G protein-coupled receptor / GPCR / receptor / partial agonist
Function / homology
Function and homology information


positive regulation of acetylcholine secretion, neurotransmission / positive regulation of circadian sleep/wake cycle, sleep / regulation of norepinephrine secretion / negative regulation of alpha-beta T cell activation / Adenosine P1 receptors / G protein-coupled adenosine receptor activity / G protein-coupled adenosine receptor signaling pathway / response to purine-containing compound / sensory perception / positive regulation of urine volume ...positive regulation of acetylcholine secretion, neurotransmission / positive regulation of circadian sleep/wake cycle, sleep / regulation of norepinephrine secretion / negative regulation of alpha-beta T cell activation / Adenosine P1 receptors / G protein-coupled adenosine receptor activity / G protein-coupled adenosine receptor signaling pathway / response to purine-containing compound / sensory perception / positive regulation of urine volume / NGF-independant TRKA activation / Surfactant metabolism / protein kinase C-activating G protein-coupled receptor signaling pathway / synaptic transmission, dopaminergic / synaptic transmission, cholinergic / inhibitory postsynaptic potential / negative regulation of vascular permeability / type 5 metabotropic glutamate receptor binding / positive regulation of glutamate secretion / blood circulation / intermediate filament / response to caffeine / eating behavior / presynaptic active zone / alpha-actinin binding / membrane depolarization / regulation of calcium ion transport / asymmetric synapse / axolemma / response to inorganic substance / cellular defense response / prepulse inhibition / phagocytosis / positive regulation of apoptotic signaling pathway / response to amphetamine / excitatory postsynaptic potential / presynaptic modulation of chemical synaptic transmission / positive regulation of synaptic transmission, glutamatergic / neuron projection morphogenesis / locomotory behavior / regulation of mitochondrial membrane potential / synaptic transmission, glutamatergic / central nervous system development / positive regulation of long-term synaptic potentiation / astrocyte activation / apoptotic signaling pathway / positive regulation of protein secretion / positive regulation of synaptic transmission, GABAergic / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / negative regulation of inflammatory response / vasodilation / blood coagulation / cell-cell signaling / presynaptic membrane / G alpha (s) signalling events / postsynaptic membrane / negative regulation of neuron apoptotic process / electron transfer activity / periplasmic space / calmodulin binding / response to xenobiotic stimulus / inflammatory response / iron ion binding / negative regulation of cell population proliferation / dendrite / neuronal cell body / glutamatergic synapse / lipid binding / apoptotic process / heme binding / protein-containing complex binding / regulation of DNA-templated transcription / enzyme binding / membrane / identical protein binding / plasma membrane
Similarity search - Function
Adenosine A2A receptor / Adenosine receptor / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / Serpentine type 7TM GPCR chemoreceptor Srsx / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family)
Similarity search - Domain/homology
CHOLESTEROL / OLEIC ACID / Chem-RVZ / Soluble cytochrome b562 / Adenosine receptor A2a
Similarity search - Component
Biological speciesHomo sapiens (human)
Escherichia coli (E. coli)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.119 Å
AuthorsVerdon, G. / Amelia, T. / van Veldhoven, J. / Falsini, M. / Liu, R. / Heitman, L. / van Westen, G. / Segala, E. / Cheng, R. / Cooke, R. ...Verdon, G. / Amelia, T. / van Veldhoven, J. / Falsini, M. / Liu, R. / Heitman, L. / van Westen, G. / Segala, E. / Cheng, R. / Cooke, R. / van der Es, D. / Ijzerman, A.
CitationJournal: J.Med.Chem. / Year: 2021
Title: Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A 2A Receptor.
Authors: Amelia, T. / van Veldhoven, J.P.D. / Falsini, M. / Liu, R. / Heitman, L.H. / van Westen, G.J.P. / Segala, E. / Verdon, G. / Cheng, R.K.Y. / Cooke, R.M. / van der Es, D. / IJzerman, A.P.
History
DepositionOct 25, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 7, 2021Provider: repository / Type: Initial release
Revision 1.1Apr 21, 2021Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Jan 31, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Adenosine receptor A2a,Soluble cytochrome b562,Adenosine receptor A2a
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,8698
Polymers47,9971
Non-polymers1,8727
Water181
1
A: Adenosine receptor A2a,Soluble cytochrome b562,Adenosine receptor A2a
hetero molecules

A: Adenosine receptor A2a,Soluble cytochrome b562,Adenosine receptor A2a
hetero molecules


Theoretical massNumber of molelcules
Total (without water)99,73716
Polymers95,9932
Non-polymers3,74414
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_577x,-y+2,-z+21
Buried area4130 Å2
ΔGint-39 kcal/mol
Surface area38370 Å2
MethodPISA
Unit cell
Length a, b, c (Å)39.541, 181.027, 140.853
Angle α, β, γ (deg.)90, 90, 90
Int Tables number20
Space group name H-MC2221

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Components

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Protein , 1 types, 1 molecules A

#1: Protein Adenosine receptor A2a,Soluble cytochrome b562,Adenosine receptor A2a / Cytochrome b-562


Mass: 47996.746 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human), (gene. exp.) Escherichia coli (E. coli)
Gene: ADORA2A, ADORA2, cybC / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P29274, UniProt: P0ABE7

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Non-polymers , 5 types, 8 molecules

#2: Chemical ChemComp-RVZ / 2-azanyl-6-(1~{H}-imidazol-2-ylmethylsulfanyl)-4-phenyl-pyridine-3,5-dicarbonitrile


Mass: 332.382 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H12N6S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-OLA / OLEIC ACID / Oleic acid


Mass: 282.461 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C18H34O2
#4: Chemical ChemComp-CLR / CHOLESTEROL / Cholesterol


Mass: 386.654 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H46O
#5: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestY

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.63 Å3/Da / Density % sol: 53.16 %
Crystal growTemperature: 300 K / Method: lipidic cubic phase
Details: 29-32% PEG 400, 0.1M tri-sodium Citrate pH = 5.3-5.4, 0.05M Sodium Thiocyanate, 2.5 % 2,5-hexanediol

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: May 17, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3.12→43.09 Å / Num. obs: 7990 / % possible obs: 92.6 % / Redundancy: 3.9 % / CC1/2: 0.992 / Net I/σ(I): 5.2
Reflection shellResolution: 3.12→3.31 Å / Num. unique obs: 399 / CC1/2: 0.309

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Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
XDSdata reduction
Aimlessdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5IU4

5iu4


Resolution: 3.119→43.09 Å / Cor.coef. Fo:Fc: 0.884 / Cor.coef. Fo:Fc free: 0.891 / Cross valid method: THROUGHOUT / SU Rfree Blow DPI: 0.509
RfactorNum. reflection% reflectionSelection details
Rfree0.2545 394 -RANDOM
Rwork0.2231 ---
obs0.2247 7990 84.5 %-
Displacement parametersBiso mean: 76.88 Å2
Baniso -1Baniso -2Baniso -3
1-7.2329 Å20 Å20 Å2
2---8.3656 Å20 Å2
3---1.1326 Å2
Refine analyzeLuzzati coordinate error obs: 0.47 Å
Refinement stepCycle: LAST / Resolution: 3.119→43.09 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2932 0 92 1 3025
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0073096HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.814211HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1055SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes508HARMONIC5
X-RAY DIFFRACTIONt_it3096HARMONIC10
X-RAY DIFFRACTIONt_chiral_improper_torsion417SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact2581SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion2.82
X-RAY DIFFRACTIONt_other_torsion18.98
LS refinement shellResolution: 3.12→3.31 Å
RfactorNum. reflection% reflection
Rfree0.2655 19 -
Rwork0.2244 --
obs0.2262 421 27.12 %
Refinement TLS params.

Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.0944-0.0075-0.12431.5453-0.29631.8306-0.0657-0.0422-0.0648-0.04220.03020.1097-0.06480.10970.03550.0266-0.0292-0.0511-0.1933-0.0083-0.000222.013188.233158.975
28.3155-1.8510.10628.3155-1.03012.51330-0.54420.3636-0.54420.5442-0.23890.3636-0.2389-0.5442-0.26270.1520.0268-0.3040.00420.304-2.1505236.372161.072
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|-1 - A|208 A|219 - A|305 A|1201 - A|1201 }A-1 - 208
2X-RAY DIFFRACTION1{ A|-1 - A|208 A|219 - A|305 A|1201 - A|1201 }A219 - 305
3X-RAY DIFFRACTION1{ A|-1 - A|208 A|219 - A|305 A|1201 - A|1201 }A1201
4X-RAY DIFFRACTION2{ A|1001 - A|1106 }A1001 - 1106

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