7VDR: Cyclin-dependent kinase 5

The structure of cyclin-dependent kinase 5 (CDK5) in complex with p25 and Compound 13. Determined by X-ray diffraction at 2.55 Å resolution. Released 9 Mar 2022.

Method: X-ray diffraction
Resolution: 2.55 Å
Organism: Homo sapiens
Chains: 4
Atoms: 7,028
Mol. weight: 114.88 kDa
Ligands: 63I
Released: 9 Mar 2022

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

Secondary structure: helices and β-sheets

7VDR contains 44 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	4-12	9	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: 15 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	4-9	6	4
β-strand	19-23	5	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	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: 7 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	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	148-154	7
α-helix	173-187	15
α-helix	198-209	12
α-helix	219-237	19
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

>7VDR_1 Cyclin-dependent-like kinase 5 (chains A, B)
SQKYEKLEKIGEGTYGTVFKAKNRETHEIVALKRVRLDDDDEGVPSSALREICLLKELKH
KNIVRLHDVLHSDKKLTLVFEFCDQDLKKYFDSCNGDLDPEIVKSFLFQLLKGLGFCHSR
NVLHRDLKPQNLLINRNGELKLADFGLARAFGIPVRCYSAEVVTLWYRPPDVLFGAKLYS
TSIDMWSAGCIFAELANAGRPLFPGNDVDDQLKRIFRLLGTPTEEQWPSMTKLPDYKPYP
MYPATTSLVNVVPKLNATGRDLLQNLLKCNPVQRISAEEALQHPYFSDFCPP

Sequence of entity 2 (C, D), FASTA

>7VDR_2 Cyclin-dependent kinase 5 activator 1, p25 (chains C, D)
MQPPPAQPPAPPASQLSGSQTGGSSSVKKAPHPAVTSAGTPKRVIVQASTSELLRCLGEF
LCRRCYRLKHLSPTDPVLWLRSVDRSLLLQGWQDQGFITPANVVFLYMLCRDVISSEVGS
DHELQAVLLTCLYLSYSYMGNEISYPLKPFLVESCKEAFWDRCLSVINLMSSKMLQINAD
PHYFTQVFSDLKNESGQEDKKRLLLGLDR

Ligands and cofactors

ID	Name	Formula	Copies
63I	(1R)-1-[7-[(2-fluoranyl-4-pyrazol-1-yl-phenyl)amino]-1,6-naphthyridin-2-yl]-1-(…	C25 H27 F N6 O	2

Water and common crystallization additives (PGE, EDO) 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
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

Browse structure collections

About this viewer

MolViewer shows 7VDR directly in your browser with nothing to install. Switch between cartoon, ball-and-stick, spacefill and surface views, color by chain, secondary structure or B-factor, measure distances, angles and dihedrals, and share or embed the view.