7VDP: Cyclin-dependent kinase 5

The structure of cyclin-dependent kinase 5 (CDK5) in complex with p25 and Compound 1. Determined by X-ray diffraction at 2.09 Å resolution. Released 9 Mar 2022.

Method: X-ray diffraction
Resolution: 2.09 Å
Organism: Homo sapiens
Chains: 4
Atoms: 7,321
Mol. weight: 115.32 kDa
Ligands: 65L
Released: 9 Mar 2022

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

Secondary structure: helices and β-sheets

7VDP contains 45 α-helices and 22 β-strands across 4 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: 15 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	4-11	8	1
β-strand	17-23	7	1
β-strand	29-36	8	1
α-helix	44-55	12
β-strand	63	1	2
β-strand	66-72	7	1
β-strand	75-81	7	1
β-strand	85-86	2	2
α-helix	87-93	7
α-helix	100-119	20
β-strand	122-123	2	3
α-helix	129-131	3
β-strand	132-134	3	2
β-strand	140-142	3	2
β-strand	149-150	2	3
α-helix	165-167	3
α-helix	170-173	4
α-helix	182-195	14
α-helix	208-219	12
α-helix	221-223	3
α-helix	230-232	3
α-helix	257-266	10
α-helix	271-273	3
α-helix	275-276	2
α-helix	277-281	5
α-helix	284-286	3

Chain B: 16 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	4-9	6	4
β-strand	17-23	7	4
β-strand	29-36	8	4
α-helix	44-55	12
β-strand	63	1	5
β-strand	66-72	7	4
β-strand	75-81	7	4
β-strand	85-86	2	5
α-helix	87-93	7
α-helix	100-119	20
β-strand	122-123	2	6
α-helix	129-131	3
β-strand	132-134	3	5
β-strand	140-142	3	5
β-strand	149-150	2	6
α-helix	165-167	3
α-helix	170-173	4
α-helix	182-195	14
α-helix	208-219	12
α-helix	221-223	3
α-helix	228-232	5
α-helix	248-250	3
α-helix	257-266	10
α-helix	271-273	3
α-helix	275-276	2
α-helix	277-281	5
α-helix	284-286	3

Chain C: 7 helices, 0 β-strands

Element	Residues	Length
α-helix	148-162	15
α-helix	172-187	16
α-helix	198-211	14
α-helix	219-237	19
α-helix	246-248	3
α-helix	254-277	24
α-helix	279-290	12

Chain D: 7 helices, 0 β-strands

Element	Residues	Length
α-helix	148-152	5
α-helix	173-187	15
α-helix	198-211	14
α-helix	220-237	18
α-helix	246-248	3
α-helix	254-277	24
α-helix	279-290	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Cyclin-dependent-like kinase 5	A, B	protein	292	Homo sapiens	Q00535 (AlphaFold model)
Cyclin-dependent kinase 5 activator 1, p25	C, D	protein	209	Homo sapiens	Q15078 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>7VDP_1 Cyclin-dependent-like kinase 5 (chains A, B)
SQKYEKLEKIGEGTYGTVFKAKNRETHEIVALKRVRLDDDDEGVPSSALREICLLKELKH
KNIVRLHDVLHSDKKLTLVFEFCDQDLKKYFDSCNGDLDPEIVKSFLFQLLKGLGFCHSR
NVLHRDLKPQNLLINRNGELKLADFGLARAFGIPVRCYSAEVVTLWYRPPDVLFGAKLYS
TSIDMWSAGCIFAELANAGRPLFPGNDVDDQLKRIFRLLGTPTEEQWPSMTKLPDYKPYP
MYPATTSLVNVVPKLNATGRDLLQNLLKCNPVQRISAEEALQHPYFSDFCPP

Sequence of entity 2 (C, D), FASTA

>7VDP_2 Cyclin-dependent kinase 5 activator 1, p25 (chains C, D)
MQPPPAQPPAPPASQLSGSQTGGSSSVKKAPHPAVTSAGTPKRVIVQASTSELLRCLGEF
LCRRCYRLKHLSPTDPVLWLRSVDRSLLLQGWQDQGFITPANVVFLYMLCRDVISSEVGS
DHELQAVLLTCLYLSYSYMGNEISYPLKPFLVESCKEAFWDRCLSVINLMSSKMLQINAD
PHYFTQVFSDLKNESGQEDKKRLLLGLDR

Ligands and cofactors

ID	Name	Formula	Copies
65L	[1-[3-fluoranyl-4-[(2-piperidin-4-yloxy-1,6-naphthyridin-7-yl)amino]phenyl]pyra…	C23 H23 F N6 O2	2

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

Primary citation

Discovery and Optimization of Highly Selective Inhibitors of CDK5. Daniels, M.H., Malojcic, G., Clugston, S.L. et al. J Med Chem (2022) 65:3575-3596. DOI 10.1021/acs.jmedchem.1c02069 · PubMed

Other PDB entries of the same protein (UniProt Q00535 (AlphaFold model), which also has an AlphaFold model), best resolution first:

4AU8 1.9 Å, Crystal structure of compound 4a in complex with cdk5, showing an unusual binding mode…
3O0G 1.95 Å, Crystal Structure of Cdk5:p25 in complex with an ATP analogue
9Q3N 2.1 Å, Crystal structure of human CDK5-cyclinB1 complex
1UNL 2.2 Å, Structural mechanism for the inhibition of CD5-p25 from the roscovitine, aloisine and…
1UNG 2.3 Å, Structural mechanism for the inhibition of CDK5-p25 by roscovitine, aloisine and…
1UNH 2.35 Å, Structural mechanism for the inhibition of CDK5-p25 by roscovitine, aloisine and…
9Q3O 2.5 Å, Crystal structure of human CDK5-cyclinB1 complex bound to AMP-PNP
7VDR 2.55 Å, The structure of cyclin-dependent kinase 5 (CDK5) in complex with p25 and Compound 13
1H4L 2.65 Å, Structure and regulation of the CDK5-p25(nck5a) complex
7VDQ 2.91 Å, The structure of cyclin-dependent kinase 5 (CDK5) in complex with p25 and Compound 7
7VDS 3.05 Å, The structure of cyclin-dependent kinase 5 (CDK5) in complex with p25 and Compound 24

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