8AOI: Specific covalent inhibitor(19) of ERK2

Specific covalent inhibitor(19) of ERK2. Determined by X-ray diffraction at 1.6 Å resolution. Released 28 Sept 2022.

Method: X-ray diffraction
Resolution: 1.6 Å
Organism: Homo sapiens
Chains: 1
Atoms: 3,319
Mol. weight: 43.25 kDa
Ligands: NX0
Released: 28 Sept 2022

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

Secondary structure: helices and β-sheets

8AOI contains 23 α-helices and 17 β-strands across 1 chain. 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: 23 helices, 17 β-strands

Element	Residues	Length	Sheet
β-strand	13-14	2	1
β-strand	17-18	2	1
β-strand	25-33	9	2
β-strand	38-44	7	2
β-strand	49-56	8	2
β-strand	59	1	3
β-strand	63	1	3
α-helix	66-77	12
β-strand	83	1	4
β-strand	88-90	3	2
β-strand	101-106	6	2
β-strand	110-111	2	4
α-helix	112-118	7
α-helix	120-122	3
α-helix	123-142	20
β-strand	145-146	2	5
α-helix	152-154	3
β-strand	155-157	3	4
β-strand	163-165	3	4
β-strand	172-173	2	5
α-helix	176-178	3
β-strand	180	1	6
α-helix	191-193	3
α-helix	196-199	4
β-strand	202	1	6
α-helix	208-223	16
α-helix	233-244	12
α-helix	247-248	2
α-helix	249-253	5
α-helix	258-266	9
α-helix	268-269	2
α-helix	271-274	4
α-helix	275-278	4
α-helix	284-293	10
α-helix	302-303	2
α-helix	304-308	5
α-helix	311-313	3
α-helix	319-321	3
α-helix	340-350	11
α-helix	352-354	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Mitogen-activated protein kinase 1	A	protein	368	Homo sapiens	P28482 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8AOI_1 Mitogen-activated protein kinase 1 (chains A)
MAHHHHHHMAAAAAAGAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNVNKVRVA
IKKISPFEHQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDL
YKLLKTQHLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLAR
VADPDHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKH
YLDQLNHILGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDK
MLTFNPHKRIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETA
RFQPGYRS

Ligands and cofactors

ID	Name	Formula	Copies
NX0	1-(2,3-dihydropyrido[2,3-b][1,4]oxazin-1-yl)propan-1-one	C10 H12 N2 O2	2

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

Primary citation

X-ray Screening of an Electrophilic Fragment Library and Application toward the Development of a Novel ERK 1/2 Covalent Inhibitor. St Denis, J.D., Chessari, G., Cleasby, A. et al. J Med Chem (2022) 65:12319-12333. DOI 10.1021/acs.jmedchem.2c01044 · PubMed

Other PDB entries of the same protein (UniProt P28482 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8AOJ 1.12 Å, Specific covalent inhibitor of ERK2
4ZZN 1.33 Å, Human ERK2 in complex with an inhibitor
6SLG 1.33 Å, Human ERK2 with ERK1/2 inhibitor, AZD0364.
5WP1 1.4 Å, Complex of ERK2 with 5,7-dihydroxychromone
4QTA 1.45 Å, Structure of human ERK2 in complex with SCH772984 revealing a novel inhibitor-induced…
4QTE 1.5 Å, Structure of ERK2 in complex with VTX-11e, 4-{2-[(2-CHLORO-4-FLUOROPHENYL)AMINO]-5-METHYL…
2Y9Q 1.55 Å, Crystal structure of human ERK2 complexed with a MAPK docking peptide
6QA3 1.57 Å, ERK2 mini-fragment binding
6QAL 1.57 Å, ERK2 mini-fragment binding
6GJD 1.58 Å, Erk2 signalling protein
6QA1 1.58 Å, ERK2 mini-fragment binding
6QAH 1.58 Å, ERK2 mini-fragment binding

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