8P74: CAK

Cryo-EM structure of CAK in complex with inhibitor ICEC0880 (ring-up conformation). Determined by electron microscopy at 2.2 Å resolution. Released 20 Mar 2024.

Method: Electron microscopy
Resolution: 2.2 Å
Organism: Homo sapiens
Chains: 3
Atoms: 5,115
Mol. weight: 87.78 kDa
Ligands: X3Z
Released: 20 Mar 2024

Explore 8P74 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8P74 contains 40 α-helices and 11 β-strands across 3 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 H: 6 helices, 0 β-strands

Element	Residues	Length
α-helix	258-262	5
α-helix	263-265	3
α-helix	271-274	4
α-helix	276-279	4
α-helix	280-285	6
α-helix	289-301	13

Chain I: 18 helices, 0 β-strands

Element	Residues	Length
α-helix	2-4	3
α-helix	6-10	5
α-helix	16-37	22
α-helix	50-70	21
α-helix	77-92	16
α-helix	101-115	15
α-helix	122-126	5
α-helix	133-153	21
α-helix	164-177	14
α-helix	184-187	4
α-helix	188-200	13
α-helix	203-205	3
α-helix	209-224	16
α-helix	229-230	2
α-helix	231-235	5
α-helix	242-260	19
α-helix	264-266	3
α-helix	267-282	16

Chain J: 16 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	14-20	7	1
β-strand	25-29	5	1
β-strand	38-41	4	1
α-helix	57-66	10
β-strand	74	1	2
β-strand	77-83	7	1
β-strand	86-92	7	1
β-strand	96-97	2	2
α-helix	98-103	6
α-helix	111-130	20
β-strand	133-134	2	3
α-helix	140-142	3
β-strand	143-145	3	2
β-strand	151-153	3	2
α-helix	156-158	3
β-strand	160-161	2	3
α-helix	176-178	3
α-helix	181-184	4
α-helix	193-208	16
α-helix	218-228	11
α-helix	240-242	3
α-helix	257-260	4
α-helix	266-275	10
α-helix	286-290	5
α-helix	293-296	4
α-helix	300-303	4
α-helix	304-306	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
CDK-activating kinase assembly factor MAT1	H	protein	93	Homo sapiens	P51948 (AlphaFold model)
Cyclin-H	I	protein	324	Homo sapiens	P51946 (AlphaFold model)
Cyclin-dependent kinase 7	J	protein	349	Homo sapiens	P50613 (AlphaFold model)

Sequence of entity 1 (H), FASTA

>8P74_1 CDK-activating kinase assembly factor MAT1 (chains H)
SNAPVTFSTGIKMGQHISLAPIHKLEEALYEYQPLQIETYGPHVPELEMLGRLGYLNHVR
AASPQDLAGGYTSSLACHRALQDAFSGLFWQPS

Sequence of entity 2 (I), FASTA

>8P74_2 Cyclin-H (chains I)
XMYHNSSQKRHWTFSSEEQLARLRADANRKFRCKAVANGKVLPNDPVFLEPHEEMTLCKY
YEKRLLEFCSVFKPAMPRSVVGTACMYFKRFYLNNSVMEYHPRIIMLTCAFLACKVDEFN
VSSPQFVGNLRESPLGQEKALEQILEYELLLIQQLNFHLIVHNPYRPFEGFLIDLKTRYP
ILENPEILRKTADDFLNRIALTDAYLLYTPSQIALTAILSSASRAGITMESYLSESLMLK
ENRTCLSQLLDIMKSMRNLVKKYEPPRSEEVAVLKQKLERCHSAELALNVITKKRKGYED
DDYVSKKSKHEEEEWTDDDLVESL

Sequence of entity 3 (J), FASTA

>8P74_3 Cyclin-dependent kinase 7 (chains J)
SNAMALDVKSRAKRYEKLDFLGEGQFATVYKARDKNTNQIVAIKKIKLGHRSEAKDGINR
TALREIKLLQELSHPNIIGLLDAFGHKSNISLVFDFMETDLEVIIKDNSLVLTPSHIKAY
MLMTLQGLEYLHQHWILHRDLKPNNLLLDENGVLKLADFGLAKSFGSPNRAYTHQVVTRW
YRAPELLFGARMYGVGVDMWAVGCILAELLLRVPFLPGDSDLDQLTRIFETLGTPTEEQW
PDMCSLPDYVTFKSFPGIPLHHIFSAAGDDLLDLIQGLFLFNPCARITATQALKMKYFSN
RPGPTPGCQLPRPNCPVETLKEQSNPALAIKRKRTEALEQGGLPKKLIF

Ligands and cofactors

ID	Name	Formula	Copies
X3Z	(2S,3S)-3-[[7-[(2-bromophenyl)methylamino]-3-propan-2-yl-pyrazolo[1,5-a]pyrimid…	C20 H26 Br N5 O3	1

Primary citation

High-resolution cryo-EM of the human CDK-activating kinase for structure-based drug design. Cushing, V.I., Koh, A.F., Feng, J. et al. Nat Commun (2024) 15:2265-2265. DOI 10.1038/s41467-024-46375-9 · PubMed

Other PDB entries of the same protein (UniProt P51948 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8P79 1.7 Å, Cryo-EM structure of CAK with averaged inhibitor density
8P77 1.8 Å, Cryo-EM structure of CAK in complex with inhibitor ICEC0943
8ORM 1.9 Å, Cryo-EM structure of CAK-THZ1
8P6V 1.9 Å, Cryo-EM structure of CAK in complex with inhibitor ICEC0942
8P6W 1.9 Å, Cryo-EM structure of CAK in complex with inhibitor BS-181
8P6X 1.9 Å, Cryo-EM structure of CAK in complex with inhibitor BS-194
8P6Y 1.9 Å, Cryo-EM structure of CAK in complex with nucleotide analogue ATPgS
8P72 1.9 Å, Cryo-EM structure of CAK in complex with inhibitor ICEC0768
8P78 1.9 Å, Cryo-EM structure of CAK in complex with inhibitor dinaciclib
8PLZ 1.9 Å, Cryo-EM structure of CAK in complex with inhibitor CT7030
8P70 2.0 Å, Cryo-EM structure of CAK in complex with inhibitor ICEC0510-S
8P71 2.0 Å, Cryo-EM structure of CAK in complex with inhibitor ICEC0574

Browse structure collections

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