7K7Z: Beta-adrenergic receptor kinase 1

Structure of a hit for G Protein Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure. Determined by X-ray diffraction at 2.61 Å resolution. Released 28 Oct 2020.

Method: X-ray diffraction
Resolution: 2.61 Å
Organism: Homo sapiens
Chains: 3
Atoms: 8,204
Mol. weight: 118.65 kDa
Ligands: W4G
Released: 28 Oct 2020

Explore 7K7Z in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7K7Z contains 43 α-helices and 50 β-strands across 3 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 35 helices, 22 β-strands

Element	Residues	Length	Sheet
α-helix	34-36	3
α-helix	39-50	12
α-helix	55-59	5
α-helix	62-74	13
α-helix	77-79	3
α-helix	80-94	15
α-helix	98-109	12
α-helix	114-117	4
α-helix	123-125	3
α-helix	126-137	12
α-helix	147-155	9
α-helix	160-166	7
α-helix	169-181	13
α-helix	188-190	3
β-strand	191-199	9	1
β-strand	204-210	7	1
β-strand	216-221	6	1
α-helix	224-230	7
α-helix	233-246	14
β-strand	254	1	2
β-strand	257-262	6	1
β-strand	267-271	5	1
β-strand	278	1	2
α-helix	279-286	8
α-helix	288-290	3
α-helix	291-310	20
β-strand	313-314	2	3
α-helix	320-322	3
β-strand	323-325	3	2
β-strand	331-333	3	2
β-strand	340-341	2	3
α-helix	371-385	15
α-helix	399-407	9
α-helix	410-411	2
α-helix	419-428	10
α-helix	433-435	3
α-helix	444-447	4
α-helix	451-453	3
α-helix	458-462	5
α-helix	467-468	2
α-helix	500-506	7
β-strand	511-512	2	1
α-helix	514-522	9
α-helix	526-547	22
β-strand	561-568	8	4
β-strand	572	1	5
β-strand	574	1	5
β-strand	577-584	8	4
β-strand	587-591	5	4
β-strand	599	1	4
β-strand	602	1	4
α-helix	603-605	3
β-strand	606-614	9	4
β-strand	617-624	8	4
β-strand	629-633	5	4
α-helix	637-658	22
α-helix	666-667	2

Chain B: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	3-24	22
α-helix	30-33	4
α-helix	38-39	2
β-strand	47-51	5	6
β-strand	58-63	6	7
β-strand	69-74	6	7
β-strand	78-83	6	7
β-strand	89-94	6	7
β-strand	100-105	6	8
β-strand	111-116	6	8
β-strand	120-125	6	8
β-strand	134-140	7	8
β-strand	146-151	6	9
β-strand	156-161	6	9
β-strand	166-170	5	9
β-strand	175-180	6	9
β-strand	187-192	6	10
β-strand	198-203	6	10
β-strand	208-212	5	10
β-strand	218-222	5	10
β-strand	229-234	6	11
β-strand	240-245	6	11
β-strand	250-254	5	11
β-strand	259-264	6	11
α-helix	272	1
β-strand	273-278	6	12
β-strand	284-289	6	12
β-strand	293-298	6	12
β-strand	304-309	6	12
β-strand	315-320	6	6
β-strand	327-331	5	6
β-strand	336-339	4	6

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	9-23	15
α-helix	30-44	15
α-helix	45-47	3
α-helix	56-58	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Beta-adrenergic receptor kinase 1	A	protein	640	Homo sapiens	P25098 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	339	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	59	Homo sapiens	P59768 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>7K7Z_1 Beta-adrenergic receptor kinase 1 (chains A)
KKILLPEPSIRSVMQKYLEDRGEVTFEKIFSQKLGYLLFRDFCLNHLEEARPLVEFYEEI
KKYEKLETEEERVARSREIFDSYIMKELLACSHPFSKSATEHVQGHLGKKQVPPDLFQPY
IEEICQNLRGDVFQKFIESDKFTRFCQWKNVELNIHLTMNDFSVHRIIGRGGFGEVYGCR
KADTGKMYAMKCLDKKRIKMKQGETLALNERIMLSLVSTGDCPFIVCMSYAFHTPDKLSF
ILDLMNGGDLHYHLSQHGVFSEADMRFYAAEIILGLEHMHNRFVVYRDLKPANILLDEHG
HVRISDLGLACDFSKKKPHASVGTHGYMAPEVLQKGVAYDSSADWFSLGCMLFKLLRGHS
PFRQHKTKDKHEIDRMTLTMAVELPDSFSPELRSLLEGLLQRDVNRRLGCLGRGAQEVKE
SPFFRSLDWQMVFLQKYPPPLIPPRGEVNAADAFDIGSFDEEDTKGIKLLDSDQELYRNF
PLTISERWQQEVAETVFDTINAETDRLEARKKAKNKQLGHEEDYALGKDCIMHGYMSKMG
NPFLTQWQRRYFYLFPNRLEWRGEGEAPQSLLTMEEIQSVEETQIKERKCLLLKIRGGKQ
FILQCDSDPELVQWKKELRDAYREAQQLVQRVPKMKNKPA

Sequence of entity 2 (B), FASTA

>7K7Z_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
SELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYAM
HWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNIC
SIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTFT
GHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNAF
ATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDALK
ADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (G), FASTA

>7K7Z_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
TASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPFREK

Ligands and cofactors

ID	Name	Formula	Copies
W4G	3-benzyl-7-(1H-pyrazol-4-yl)quinazolin-4(3H)-one	C18 H14 N4 O	1

Primary citation

Hit-to-lead optimization and discovery of a potent, and orally bioavailable G protein coupled receptor kinase 2 (GRK2) inhibitor. Xu, G., Gaul, M.D., Liu, Z. et al. Bioorg Med Chem Lett (2020) 30:127602-127602. DOI 10.1016/j.bmcl.2020.127602 · PubMed

Other PDB entries of the same protein (UniProt P25098 (AlphaFold model), which also has an AlphaFold model), best resolution first:

3V5W 2.07 Å, Human G Protein-Coupled Receptor Kinase 2 in Complex with Soluble Gbetagamma Subunits…
5UKL 2.15 Å, Human GRK2 in complex with Gbetagamma subunits and CCG222886 (14bd)
5WG4 2.31 Å, Human GRK2 in complex with Gbetagamma subunits and CCG257284
4MK0 2.4 Å, Crystal structure of G protein-coupled receptor kinase 2 in complex with a a rationally…
6U7C 2.44 Å, Human GRK2 in complex with Gbetagamma subunits and CCG258747
7K7L 2.54 Å, Structure of a hit for G Protein Coupled Receptor Kinase 2 (GRK2) Inhibitor for the…
4PNK 2.56 Å, G protein-coupled receptor kinase 2 in complex with GSK180736A
5UKK 2.6 Å, Human GRK2 in complex with human G-beta-gamma subunits and CCG211998 (14ak)
7PWD 2.6 Å, Structure of an inhibited GRK2-G-beta and G-gamma complex
5UVC 2.65 Å, Design, Synthesis, and Evaluation of the First Selective and Potent G-protein-Coupled…
5UUU 2.7 Å, Design, Synthesis, and Evaluation of the First Selective and Potent G-protein-Coupled…
6C2Y 2.74 Å, Human GRK2 in complex with Gbetagamma subunits and CCG257142

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