7KIA: FGFR2 kinase domain gatekeeper mutant V564F

Crystal structure of FGFR2 kinase domain gatekeeper mutant V564F in complex with covalent compound 19. Determined by X-ray diffraction at 2.22 Å resolution. Released 10 Feb 2021.

Method: X-ray diffraction
Resolution: 2.22 Å
Organism: Homo sapiens
Chains: 2
Atoms: 4,952
Mol. weight: 72.05 kDa
Ligands: FLC, WFD
Released: 10 Feb 2021

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

Secondary structure: helices and β-sheets

7KIA contains 35 α-helices and 26 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: 17 helices, 13 β-strands

Element	Residues	Length	Sheet
α-helix	468-470	3
β-strand	475	1	1
α-helix	478-480	3
β-strand	481-490	10	1
β-strand	493-501	9	1
β-strand	511-518	8	1
α-helix	525-541	17
β-strand	547	1	2
α-helix	548-549	2
β-strand	550-554	5	1
β-strand	561-565	5	1
β-strand	571	1	2
α-helix	572-577	6
α-helix	600-619	20
β-strand	622-623	2	3
α-helix	629-631	3
β-strand	632-634	3	2
β-strand	640-642	3	2
β-strand	649-650	2	3
β-strand	666	1	4
α-helix	667-669	3
α-helix	672-676	5
α-helix	682-697	16
α-helix	701-702	2
α-helix	709-717	9
α-helix	722-725	4
α-helix	730-739	10
α-helix	744-746	3
α-helix	748-749	2
α-helix	750-763	14

Chain B: 18 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	475	1	5
α-helix	478-480	3
β-strand	481-490	10	5
β-strand	493-501	9	5
β-strand	511-518	8	5
β-strand	524	1	4
α-helix	525-541	17
β-strand	547	1	6
α-helix	548-549	2
β-strand	550-554	5	5
β-strand	561-565	5	5
β-strand	571	1	6
α-helix	572-577	6
α-helix	597-599	3
α-helix	600-619	20
β-strand	622-623	2	7
α-helix	629-631	3
β-strand	632-634	3	6
β-strand	640-642	3	6
β-strand	649-650	2	7
α-helix	667-669	3
α-helix	672-676	5
α-helix	682-697	16
α-helix	701-702	2
α-helix	709-711	3
α-helix	712-717	6
α-helix	722-725	4
α-helix	730-739	10
α-helix	744-746	3
α-helix	748-749	2
α-helix	750-765	16

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Fibroblast growth factor receptor 2	A, B	protein	308	Homo sapiens	P21802 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>7KIA_1 Fibroblast growth factor receptor 2 (chains A, B)
AGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAVTVAVKMLK
DDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYVIFEYASKGNLREYLRARR
PPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVM
KIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLG
GSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRI
LTLTTNEE

Ligands and cofactors

ID	Name	Formula	Copies
FLC	Citrate anion	C6 H5 O7	2
WFD	1-[4-(4-{4-(4-methylpiperazin-1-yl)-6-[(3-methyl-1H-pyrazol-5-yl)amino]pyrimidi…	C27 H34 N8 O	2

Water and common crystallization additives (NA) are not listed.

Primary citation

Discovery of Aminopyrazole Derivatives as Potent Inhibitors of Wild-Type and Gatekeeper Mutant FGFR2 and 3. Brawn, R.A., Cook, A., Omoto, K. et al. ACS Med Chem Lett (2021) 12:93-98. DOI 10.1021/acsmedchemlett.0c00517 · PubMed

Other PDB entries of the same protein (UniProt P21802 (AlphaFold model), which also has an AlphaFold model), best resolution first:

10OU 1.77 Å, FGFR2 mutant D650V with compound 12
2PVF 1.8 Å, Crystal Structure of Tyrosine Phosphorylated Activated FGF Receptor 2 (FGFR2) Kinase…
3B2T 1.8 Å, Structure of phosphotransferase
4J99 1.85 Å, Crystal Structure of FGF Receptor 2 (FGFR2) Kinase Domain Harboring the Gain-of-Function…
10OO 1.85 Å, FGFR2 mutant D650V with compound 4 (AZD3463)
5UGL 1.86 Å, Crystal Structure of FGF Receptor 2 Tyrosine Kinase Domain Harboring the D650V…
3CAF 1.96 Å, Crystal Structure of hFGFR2 D2 Domain
10OQ 1.98 Å, FGFR2 mutant D650V with compound 6
9U7S 1.99 Å, FGFR2 kinase domain with a macrocyclic compound 8r
3CLY 2.0 Å, Crystal Structure of FGF Receptor 2 (FGFR2) Kinase Domains Trapped in…
8W3D 2.04 Å, TAS-120 covalent structure with FGFR2 molecular brake mutant
5UI0 2.05 Å, Crystal Structure of the Tyrosine Kinase Domain of FGF Receptor 2 harboring an…

Browse structure collections

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