8PQE: C-KIT kinase domain

c-KIT kinase domain in complex with avapritinib derivative 11. Determined by X-ray diffraction at 2.0 Å resolution. Released 27 Dec 2023.

Method: X-ray diffraction
Resolution: 2.0 Å
Organism: Homo sapiens
Chains: 2
Atoms: 4,607
Mol. weight: 75.67 kDa
Ligands: 9WU
Released: 27 Dec 2023

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

Secondary structure: helices and β-sheets

8PQE contains 38 α-helices and 22 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: 19 helices, 10 β-strands

Element	Residues	Length	Sheet
α-helix	573-575	3
α-helix	577-579	3
α-helix	580-582	3
β-strand	583	1	1
α-helix	586-588	3
β-strand	589-597	9	1
β-strand	601-609	9	1
β-strand	617-625	9	1
α-helix	626	1
α-helix	631-647	17
β-strand	653	1	2
β-strand	656-660	5	1
β-strand	667-671	5	1
β-strand	677	1	2
α-helix	678-684	7
α-helix	766-785	20
α-helix	795-797	3
β-strand	798-801	4	2
β-strand	805-808	4	2
α-helix	833-835	3
α-helix	838-843	6
α-helix	848-863	16
α-helix	867-868	2
α-helix	877-885	9
α-helix	889-892	4
α-helix	897-906	10
α-helix	911-913	3
α-helix	915-916	2
α-helix	917-929	13

Chain B: 19 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	573-575	3
α-helix	577-579	3
α-helix	580-582	3
β-strand	583	1	3
α-helix	586-588	3
β-strand	589-597	9	3
β-strand	601-609	9	3
β-strand	617-625	9	3
α-helix	631-647	17
β-strand	653	1	4
β-strand	656-660	5	3
β-strand	667-671	5	3
β-strand	677	1	4
α-helix	678-685	8
α-helix	766-785	20
β-strand	789	1	5
α-helix	795-797	3
β-strand	798-801	4	4
α-helix	802-804	3
β-strand	805-808	4	4
β-strand	815	1	5
α-helix	833-835	3
α-helix	838-843	6
α-helix	848-863	16
α-helix	867-868	2
α-helix	877-885	9
α-helix	889-892	4
α-helix	897-906	10
α-helix	911-913	3
α-helix	915-916	2
α-helix	917-929	13

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Mast/stem cell growth factor receptor Kit	A, B	protein	327	Homo sapiens	P10721 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>8PQE_1 Mast/stem cell growth factor receptor Kit (chains A, B)
GSMPMYEVQWKVVEESNGNNYSYIDPTQLPYDHKWEFPRNRLSFGKTLGAGAFGKVVEAT
AQGLIKSDAAMTVAVKMLKPSAHSTEREALMSELKVLSYLGNHENIVNLLGACTHGGPTL
VITEYCCYGDLLNFLRRKRDEFVPYKVAPEDLYKDFLTLEHLLSFSYQVAKGMAFLASKN
CIHRDLAARNILLTHGNITKICDFGLARDIKNDSNYVDKGNARLPVKWMAPESIFNSVYT
FESDVWSYGIFLWELFSLGSSPYPGMPVDSKFYKMIKEGFRMSSPEYAPAEMYDIMKTCW
DADPDKRPTFKQIVQDIEKQISESTNH

Ligands and cofactors

ID	Name	Formula	Copies
9WU	~{N}-[(1~{S})-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f…	C29 H29 F N10 O	2

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

Primary citation

Avapritinib-based SAR studies unveil a binding pocket in KIT and PDGFRA. Teuber, A., Schulz, T., Fletcher, B.S. et al. Nat Commun (2024) 15:63-63. DOI 10.1038/s41467-023-44376-8 · PubMed

Other PDB entries of the same protein (UniProt P10721 (AlphaFold model), which also has an AlphaFold model), best resolution first:

2VIF 1.45 Å, Crystal structure of SOCS6 SH2 domain in complex with a c-KIT phosphopeptide
8PQD 1.5 Å, c-KIT kinase domain in complex with avapritinib derivative 10
8S14 1.5 Å, c-KIT kinase domain in complex with sunitinib
1T46 1.6 Å, Structural basis for the autoinhibition and sti-571 inhibition of C-kit tyrosine kinase
3G0E 1.6 Å, KIT kinase domain in complex with sunitinib
8PQA 1.65 Å, c-KIT kinase domain in complex with avapritinib derivative 4
9TFD 1.65 Å, KIT kinase domain in complex with a pyrrolotriazine-based compound (11)
8PQ9 1.7 Å, c-KIT kinase domain in complex with avapritinib
9TFE 1.7 Å, KIT kinase domain in complex with an aminopyrimidine-based compound (15)
9TFG 1.7 Å, KIT kinase domain in complex with a 6-,7-dimethoxyquinoline-based compound (19)
9TFH 1.7 Å, KIT kinase domain in complex with a 7-methylquinazoline-based compound (25)
9TFK 1.7 Å, KIT kinase domain in complex with a quinoline-3-carbonitrile-based compound (38)

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