8SV9: ULK1 kinase domain with inhibitor MR-2088

Crystal structure of ULK1 kinase domain with inhibitor MR-2088. Determined by X-ray diffraction at 2.3 Å resolution. Released 27 Mar 2024.

Method: X-ray diffraction
Resolution: 2.3 Å
Organism: Homo sapiens
Chains: 2
Atoms: 4,647
Mol. weight: 65.74 kDa
Ligands: WXH
Released: 27 Mar 2024

Explore 8SV9 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8SV9 contains 24 α-helices and 28 β-strands across 2 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: 12 helices, 14 β-strands

Element	Residues	Length	Sheet
β-strand	9-11	3	1
β-strand	14-24	11	1
β-strand	29-35	7	1
β-strand	42-47	6	1
α-helix	50-52	3
α-helix	53-67	15
β-strand	75	1	2
β-strand	78-83	6	1
β-strand	88-93	6	1
β-strand	99	1	2
α-helix	100-107	8
α-helix	112-132	21
β-strand	134-135	2	3
α-helix	141-143	3
β-strand	144-147	4	2
β-strand	160-163	4	2
β-strand	170-171	2	3
β-strand	178	1	4
α-helix	185-187	3
α-helix	190-193	4
β-strand	198	1	4
α-helix	201-216	16
α-helix	226-235	10
α-helix	249-258	10
α-helix	269-273	5
α-helix	276-278	3

Chain B: 12 helices, 14 β-strands

Element	Residues	Length	Sheet
β-strand	9-11	3	5
β-strand	14-25	12	5
β-strand	28-35	8	5
β-strand	42-47	6	5
α-helix	53-67	15
β-strand	75	1	6
β-strand	78-83	6	5
β-strand	88-93	6	5
β-strand	99	1	6
α-helix	100-107	8
α-helix	112-132	21
β-strand	134-135	2	7
α-helix	141-143	3
β-strand	144-147	4	6
α-helix	156-158	3
β-strand	160-163	4	6
β-strand	170-171	2	7
β-strand	178	1	8
α-helix	185-187	3
α-helix	190-193	4
β-strand	198	1	8
α-helix	201-216	16
α-helix	226-235	10
α-helix	249-258	10
α-helix	269-273	5
α-helix	276-278	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Serine/threonine-protein kinase ULK1	A, B	protein	283	Homo sapiens	O75385 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>8SV9_1 Serine/threonine-protein kinase ULK1 (chains A, B)
MEPGRGGTETVGKFEFSRKDLIGHGAFAVVFKGRHRAAHDLEVAVKCINKKNLAKSQTLL
GKEIKILKELKHENIVALYDFQEMANSVYLVMEYCNGGDLADYLHAMRTLSEDTIRLFLQ
QIAGAMRLLHSKGIIHRDLKPQNILLSNPAGRRANPNSIRVKIADFGFARYLQSNMMAAT
LCGSPMYMAPEVIMSQHYDGKADLWSIGTIVYQCLTGKAPFQASSPQDLRLFYEKNKTLV
PTIPRETSAPLRQLLLALLQRNHKDRMDFDEFFHHPFLDASPS

Ligands and cofactors

ID	Name	Formula	Copies
WXH	(4P)-4-[(2P)-2-(1,2,5,6-tetrahydropyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-…	C19 H17 F3 N4 O S	2

Water and common crystallization additives (EDO, SO4) are not listed.

Primary citation

Development of potent and selective ULK1/2 inhibitors based on 7-azaindole scaffold with favorable in vivo properties. Morozova, A., Chan, S.C., Bayle, S. et al. Eur J Med Chem (2024) 266:116101-116101. DOI 10.1016/j.ejmech.2023.116101 · PubMed

Other PDB entries of the same protein (UniProt O75385 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6HYO 1.07 Å, Structure of ULK1 LIR motif bound to GABARAP
4WNO 1.56 Å, Structure of ULK1 bound to an inhibitor
6MNH 1.73 Å, ULK1 Unc-51 like autophagy activating kinase in complex with inhibitor BTC
5CI7 1.74 Å, Structure of ULK1 bound to a selective inhibitor
6QAS 1.75 Å, Crystal structure of ULK1 in complexed with PF-03814735
8P5I 1.83 Å, Kinase domain of mutant human ULK1 in complex with compound XMD-17-51
8P5L 1.84 Å, Kinase domain of mutant human ULK1 in complex with compound MRT67307
4WNP 1.88 Å, Structure of ULK1 bound to a potent inhibitor
8P5H 1.94 Å, Kinase domain of mutant human ULK1 in complex with compound CCT241533
9SE8 2.0 Å, Crystal structure of ULK1 in complex with inhibitor SBP-5147
8P5G 2.02 Å, Kinase domain of wild type human ULK1 in complex with compound CCT241533
9F32 2.1 Å, Crystal structure of ULK1 with a covalent compound GCL 99

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