7VDS: Cyclin-dependent kinase 5

The structure of cyclin-dependent kinase 5 (CDK5) in complex with p25 and Compound 24. Determined by X-ray diffraction at 3.05 Å resolution. Released 9 Mar 2022.

Method: X-ray diffraction
Resolution: 3.05 Å
Organism: Homo sapiens
Chains: 4
Atoms: 7,215
Mol. weight: 116.42 kDa
Ligands: 61U
Released: 9 Mar 2022

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

Secondary structure: helices and β-sheets

7VDS contains 42 α-helices and 24 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, 12 β-strands

Element	Residues	Length	Sheet
β-strand	4-12	9	1
β-strand	17-23	7	1
β-strand	29-36	8	1
α-helix	44-55	12
β-strand	60	1	2
β-strand	63	1	2
β-strand	66-72	7	1
β-strand	75-81	7	1
α-helix	82	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	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: 15 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	4-6	3	4
β-strand	17-23	7	4
β-strand	29-35	7	4
α-helix	44-55	12
β-strand	60	1	5
β-strand	63	1	5
β-strand	66-72	7	4
β-strand	75-81	7	4
α-helix	82	1
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	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 C: 6 helices, 0 β-strands

Element	Residues	Length
α-helix	148-162	15
α-helix	173-187	15
α-helix	198-211	14
α-helix	219-237	19
α-helix	254-277	24
α-helix	279-290	12

Chain D: 6 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	254-277	24
α-helix	279-290	12

Molecules and chains

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

Sequence of entity 1 (A, B), FASTA

>7VDS_1 Cyclin-dependent-like kinase 5, p25 (chains A, B)
SQKYEKLEKIGEGTYGTVFKAKNRETHEIVALKRVRLDDDDEGVPSSALREICLLKELKH
KNIVRLHDVLHSDKKLTLVFEFCDQDLKKYFDSCNGDLDPEIVKSFLFQLLKGLGFCHSR
NVLHRDLKPQNLLINRNGELKLADFGLARAFGIPVRCYSAEVVTLWYRPPDVLFGAKLYS
TSIDMWSAGCIFAELANAGRPLFPGNDVDDQLKRIFRLLGTPTEEQWPSMTKLPDYKPYP
MYPATTSLVNVVPKLNATGRDLLQNLLKCNPVQRISAEEALQHPYFSDFCPP

Sequence of entity 2 (C, D), FASTA

>7VDS_2 Cyclin-dependent kinase 5 activator 1 (chains C, D)
MQPPPAQPPAPPASQLSGSQTGGSSSVKKAPHPAVTSAGTPKRVIVQASTSELLRCLGEF
LCRRCYRLKHLSPTDPVLWLRSVDRSLLLQGWQDQGFITPANVVFLYMLCRDVISSEVGS
DHELQAVLLTCLYLSYSYMGNEISYPLKPFLVESCKEAFWDRCLSVINLMSSKMLQINAD
PHYFTQVFSDLKNESGQEDKKRLLLGLDR

Ligands and cofactors

ID	Name	Formula	Copies
61U	5-fluoranyl-4-[[2-[(1R)-1-(1-methylpiperidin-4-yl)-1-oxidanyl-ethyl]-1,6-naphth…	C27 H31 F N6 O2	1

Water and common crystallization additives (GOL, EDO, CL) 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
7VDP 2.09 Å, The structure of cyclin-dependent kinase 5 (CDK5) in complex with p25 and Compound 1
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

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