9C1R: Mutant cMET D1228N kinase domain

Crystal structure of mutant cMET D1228N kinase domain in complex with inhibitor compound 13. Determined by X-ray diffraction at 1.59 Å resolution. Released 21 Aug 2024.

Method: X-ray diffraction
Resolution: 1.59 Å
Organism: Homo sapiens
Chains: 1
Atoms: 2,741
Mol. weight: 35.65 kDa
Ligands: A1ATS
Released: 21 Aug 2024

Explore 9C1R in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9C1R contains 19 α-helices and 10 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: 19 helices, 10 β-strands

Element	Residues	Length	Sheet
α-helix	1048-1050	3
α-helix	1055-1057	3
α-helix	1060-1068	9
β-strand	1070-1071	2	1
α-helix	1073-1075	3
β-strand	1076-1086	11	1
β-strand	1090-1098	9	1
β-strand	1104-1112	9	1
α-helix	1118-1129	12
β-strand	1139	1	2
β-strand	1144-1146	3	1
β-strand	1154-1158	5	1
β-strand	1164	1	2
α-helix	1165-1170	6
α-helix	1178-1197	20
α-helix	1207-1209	3
β-strand	1210-1212	3	2
β-strand	1218-1220	3	2
α-helix	1247-1249	3
α-helix	1252-1257	6
α-helix	1262-1277	16
α-helix	1281-1282	2
α-helix	1287-1289	3
α-helix	1292-1297	6
α-helix	1302-1305	4
α-helix	1310-1319	10
α-helix	1324-1326	3
α-helix	1328-1329	2
α-helix	1330-1343	14

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Hepatocyte growth factor receptor	A	protein	307	Homo sapiens	P08581 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>9C1R_1 Hepatocyte growth factor receptor (chains A)
MQNTVHIDLSALNPELVQAVQHVVIGPSSLIVHFNEVIGRGHFGCVYHGTLLDNDGKKIH
CAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNVLSLLGICLRSEGSPLVVLPYMKHGDLR
NFIRNETHNPTVKDLIGFGLQVAKGMKYLASKKFVHRDLAARNCMLDEKFTVKVADFGLA
RNMYDKEYYSVHNKTGAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPD
VNTFDITVYLLQGRRLLQPEYCPDPLYEVMLKCWHPKAEMRPSFSELVSRISAIFSTFIG
EHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
A1ATS	N-(2,5-difluoro-4-{[(1s,3S)-3-(1-methyl-1H-pyrazol-3-yl)cyclobutyl][(8R)-pyrazo…	C30 H23 F3 N10 O2	1

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

Primary citation

Discovery of Pyrazolopyrazines as Selective, Potent, and Mutant-Active MET Inhibitors with Intracranial Efficacy. Bumpers, Q.A., Pipal, R.W., Benz-Weeden, A.M. et al. J Med Chem (2024) 67:14466-14477. DOI 10.1021/acs.jmedchem.4c01232 · PubMed

Other PDB entries of the same protein (UniProt P08581 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9T6K 1.13 Å, Crystal structure of wild-type c-MET bound by glumetinib.
9T0D 1.2 Å, Crystal structure of wild-type c-MET bound by glesatinib
4R1V 1.2 Å, Identification and optimization of pyridazinones as potent and selective c-Met kinase…
9SXJ 1.31 Å, Crystal structure of wild-type c-MET bound by capmatinib.
3BUX 1.35 Å, Crystal structure of c-Cbl-TKB domain complexed with its binding motif in c-Met
3F66 1.4 Å, Human c-Met Kinase in complex with quinoxaline inhibitor
3ZCL 1.4 Å, X-ray Structure of c-Met kinase in complex with inhibitor…
9T08 1.46 Å, Crystal structure of wild-type c-MET bound by sitravatinib.
3DKC 1.52 Å, Structure of MET receptor tyrosine kinase in complex with ATP
9T0B 1.54 Å, Crystal structure of D1228V c-MET bound by sitravatinib.
3Q6U 1.6 Å, Structure of the apo MET receptor kinase in the dually-phosphorylated, activated state
9T3Q 1.63 Å, Crystal structure of D1228V c-MET bound by cabozantinib.

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