6FET

Crystal structure of human phosphodiesterase 4D2 catalytic domain with inhibitor NPD-1439

PDB DOI: https://doi.org/10.2210/pdb6FET/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2018-01-03 Released: 2019-04-24
Deposition Author(s): Singh, A.K., Brown, D.G.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.88 Å
R-Value Free: 0.199
R-Value Work: 0.171
R-Value Observed: 0.173

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

hPDE4D2 structure with inhibitor NPD-1439

Salado, I.G., Moreno, C., Sakaine, G., Singh, A.K., Blaazer, A.R., Siderius, M., Matheeussen, A., Gul, S., Maes, L., Leurs, R., Brown, D.G., Augustyns, K.

To be published.

Macromolecule Content

Total Structure Weight: 176.36 kDa
Atom Count: 11,731
Modelled Residue Count: 1,300
Deposited Residue Count: 1,456
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
cAMP-specific 3',5'-cyclic phosphodiesterase 4D	A, B, C, D	364	Homo sapiens	Mutation(s): 0 Gene Names: PDE4D, DPDE3 EC: 3.1.4.53
UniProt & NIH Common Fund Data Resources
Find proteins for Q08499 (Homo sapiens) Explore Q08499 Go to UniProtKB: Q08499
PHAROS: Q08499 GTEx: ENSG00000113448
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q08499
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 8 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
D68 (Subject of Investigation/LOI) Query on D68 Download Ideal Coordinates CCD File SDF format, chain KC [auth D] SDF format, chain NB [auth C] SDF format, chain QA [auth B] SDF format, chain U [auth A] MOL2 format, chain KC [auth D] MOL2 format, chain NB [auth C] MOL2 format, chain QA [auth B] MOL2 format, chain U [auth A] mmCIF format, chain KC [auth D] mmCIF format, chain NB [auth C] mmCIF format, chain QA [auth B] mmCIF format, chain U [auth A]	KC [auth D], NB [auth C], QA [auth B], U [auth A]	1-(2-{4-[(4aS,8aR)-4-[3,4-bis(difluoromethoxy)phenyl]-1-oxo-1,2,4a,5,8,8a-hexahydrophthalazin-2-yl]piperidin-1-yl}-2-oxoethyl)-4,4-dimethylpiperidine-2,6-dione C₃₀ H₃₄ F₄ N₄ O₆ WVAQTVIALKSAMT-VQTJNVASSA-N		Interactions Focus chain KC [auth D] Focus chain NB [auth C] Focus chain QA [auth B] Focus chain U [auth A] Interactions & Density Focus chain KC [auth D] Focus chain NB [auth C] Focus chain QA [auth B] Focus chain U [auth A]
EPE Query on EPE Download Ideal Coordinates CCD File SDF format, chain JA [auth B] SDF format, chain KB [auth C] SDF format, chain LC [auth D] SDF format, chain PA [auth B] SDF format, chain V [auth A] MOL2 format, chain JA [auth B] MOL2 format, chain KB [auth C] MOL2 format, chain LC [auth D] MOL2 format, chain PA [auth B] MOL2 format, chain V [auth A] mmCIF format, chain JA [auth B] mmCIF format, chain KB [auth C] mmCIF format, chain LC [auth D] mmCIF format, chain PA [auth B] mmCIF format, chain V [auth A]	JA [auth B], KB [auth C], LC [auth D], PA [auth B], V [auth A]	4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID C₈ H₁₈ N₂ O₄ S JKMHFZQWWAIEOD-UHFFFAOYSA-N		Interactions Focus chain JA [auth B] Focus chain KB [auth C] Focus chain LC [auth D] Focus chain PA [auth B] Focus chain V [auth A] Interactions & Density Focus chain JA [auth B] Focus chain KB [auth C] Focus chain LC [auth D] Focus chain PA [auth B] Focus chain V [auth A]
PG4 Query on PG4 Download Ideal Coordinates CCD File SDF format, chain MB [auth C] SDF format, chain SB [auth D] MOL2 format, chain MB [auth C] MOL2 format, chain SB [auth D] mmCIF format, chain MB [auth C] mmCIF format, chain SB [auth D]	MB [auth C], SB [auth D]	TETRAETHYLENE GLYCOL C₈ H₁₈ O₅ UWHCKJMYHZGTIT-UHFFFAOYSA-N		Interactions Focus chain MB [auth C] Focus chain SB [auth D] Interactions & Density Focus chain MB [auth C] Focus chain SB [auth D]
PEG Query on PEG Download Ideal Coordinates CCD File SDF format, chain JB [auth C] SDF format, chain JC [auth D] SDF format, chain N [auth A] SDF format, chain OA [auth B] MOL2 format, chain JB [auth C] MOL2 format, chain JC [auth D] MOL2 format, chain N [auth A] MOL2 format, chain OA [auth B] mmCIF format, chain JB [auth C] mmCIF format, chain JC [auth D] mmCIF format, chain N [auth A] mmCIF format, chain OA [auth B]	JB [auth C], JC [auth D], N [auth A], OA [auth B]	DI(HYDROXYETHYL)ETHER C₄ H₁₀ O₃ MTHSVFCYNBDYFN-UHFFFAOYSA-N		Interactions Focus chain JB [auth C] Focus chain JC [auth D] Focus chain N [auth A] Focus chain OA [auth B] Interactions & Density Focus chain JB [auth C] Focus chain JC [auth D] Focus chain N [auth A] Focus chain OA [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain CB [auth C] SDF format, chain DA [auth B] SDF format, chain E [auth A] SDF format, chain UB [auth D] MOL2 format, chain CB [auth C] MOL2 format, chain DA [auth B] MOL2 format, chain E [auth A] MOL2 format, chain UB [auth D] mmCIF format, chain CB [auth C] mmCIF format, chain DA [auth B] mmCIF format, chain E [auth A] mmCIF format, chain UB [auth D]	CB [auth C], DA [auth B], E [auth A], UB [auth D]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain CB [auth C] Focus chain DA [auth B] Focus chain E [auth A] Focus chain UB [auth D] Interactions & Density Focus chain CB [auth C] Focus chain DA [auth B] Focus chain E [auth A] Focus chain UB [auth D]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain AA [auth A] SDF format, chain AB [auth C] SDF format, chain AC [auth D] SDF format, chain BA [auth A] SDF format, chain BB [auth C] SDF format, chain BC [auth D] SDF format, chain CC [auth D] SDF format, chain DC [auth D] SDF format, chain EB [auth C] SDF format, chain EC [auth D] SDF format, chain FA [auth B] SDF format, chain FB [auth C] SDF format, chain FC [auth D] SDF format, chain G [auth A] SDF format, chain GA [auth B] SDF format, chain GB [auth C] SDF format, chain GC [auth D] SDF format, chain H [auth A] SDF format, chain HA [auth B] SDF format, chain HB [auth C] SDF format, chain HC [auth D] SDF format, chain I [auth A] SDF format, chain IA [auth B] SDF format, chain IB [auth C] SDF format, chain IC [auth D] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain KA [auth B] SDF format, chain L [auth A] SDF format, chain LA [auth B] SDF format, chain LB [auth C] SDF format, chain M [auth A] SDF format, chain MA [auth B] SDF format, chain MC [auth D] SDF format, chain NA [auth B] SDF format, chain NC [auth D] SDF format, chain O [auth A] SDF format, chain OB [auth C] SDF format, chain OC [auth D] SDF format, chain P [auth A] SDF format, chain PB [auth C] SDF format, chain PC [auth D] SDF format, chain Q [auth A] SDF format, chain QB [auth C] SDF format, chain QC [auth D] SDF format, chain R [auth A] SDF format, chain RA [auth B] SDF format, chain RB [auth D] SDF format, chain S [auth A] SDF format, chain SA [auth B] SDF format, chain T [auth A] SDF format, chain TA [auth B] SDF format, chain TB [auth D] SDF format, chain UA [auth B] SDF format, chain VA [auth B] SDF format, chain W [auth A] SDF format, chain WA [auth B] SDF format, chain WB [auth D] SDF format, chain X [auth A] SDF format, chain XA [auth B] SDF format, chain XB [auth D] SDF format, chain Y [auth A] SDF format, chain YA [auth B] SDF format, chain YB [auth D] SDF format, chain Z [auth A] SDF format, chain ZA [auth C] SDF format, chain ZB [auth D] MOL2 format, chain AA [auth A] MOL2 format, chain AB [auth C] MOL2 format, chain AC [auth D] MOL2 format, chain BA [auth A] MOL2 format, chain BB [auth C] MOL2 format, chain BC [auth D] MOL2 format, chain CC [auth D] MOL2 format, chain DC [auth D] MOL2 format, chain EB [auth C] MOL2 format, chain EC [auth D] MOL2 format, chain FA [auth B] MOL2 format, chain FB [auth C] MOL2 format, chain FC [auth D] MOL2 format, chain G [auth A] MOL2 format, chain GA [auth B] MOL2 format, chain GB [auth C] MOL2 format, chain GC [auth D] MOL2 format, chain H [auth A] MOL2 format, chain HA [auth B] MOL2 format, chain HB [auth C] MOL2 format, chain HC [auth D] MOL2 format, chain I [auth A] MOL2 format, chain IA [auth B] MOL2 format, chain IB [auth C] MOL2 format, chain IC [auth D] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain KA [auth B] MOL2 format, chain L [auth A] MOL2 format, chain LA [auth B] MOL2 format, chain LB [auth C] MOL2 format, chain M [auth A] MOL2 format, chain MA [auth B] MOL2 format, chain MC [auth D] MOL2 format, chain NA [auth B] MOL2 format, chain NC [auth D] MOL2 format, chain O [auth A] MOL2 format, chain OB [auth C] MOL2 format, chain OC [auth D] MOL2 format, chain P [auth A] MOL2 format, chain PB [auth C] MOL2 format, chain PC [auth D] MOL2 format, chain Q [auth A] MOL2 format, chain QB [auth C] MOL2 format, chain QC [auth D] MOL2 format, chain R [auth A] MOL2 format, chain RA [auth B] MOL2 format, chain RB [auth D] MOL2 format, chain S [auth A] MOL2 format, chain SA [auth B] MOL2 format, chain T [auth A] MOL2 format, chain TA [auth B] MOL2 format, chain TB [auth D] MOL2 format, chain UA [auth B] MOL2 format, chain VA [auth B] MOL2 format, chain W [auth A] MOL2 format, chain WA [auth B] MOL2 format, chain WB [auth D] MOL2 format, chain X [auth A] MOL2 format, chain XA [auth B] MOL2 format, chain XB [auth D] MOL2 format, chain Y [auth A] MOL2 format, chain YA [auth B] MOL2 format, chain YB [auth D] MOL2 format, chain Z [auth A] MOL2 format, chain ZA [auth C] MOL2 format, chain ZB [auth D] mmCIF format, chain AA [auth A] mmCIF format, chain AB [auth C] mmCIF format, chain AC [auth D] mmCIF format, chain BA [auth A] mmCIF format, chain BB [auth C] mmCIF format, chain BC [auth D] mmCIF format, chain CC [auth D] mmCIF format, chain DC [auth D] mmCIF format, chain EB [auth C] mmCIF format, chain EC [auth D] mmCIF format, chain FA [auth B] mmCIF format, chain FB [auth C] mmCIF format, chain FC [auth D] mmCIF format, chain G [auth A] mmCIF format, chain GA [auth B] mmCIF format, chain GB [auth C] mmCIF format, chain GC [auth D] mmCIF format, chain H [auth A] mmCIF format, chain HA [auth B] mmCIF format, chain HB [auth C] mmCIF format, chain HC [auth D] mmCIF format, chain I [auth A] mmCIF format, chain IA [auth B] mmCIF format, chain IB [auth C] mmCIF format, chain IC [auth D] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain KA [auth B] mmCIF format, chain L [auth A] mmCIF format, chain LA [auth B] mmCIF format, chain LB [auth C] mmCIF format, chain M [auth A] mmCIF format, chain MA [auth B] mmCIF format, chain MC [auth D] mmCIF format, chain NA [auth B] mmCIF format, chain NC [auth D] mmCIF format, chain O [auth A] mmCIF format, chain OB [auth C] mmCIF format, chain OC [auth D] mmCIF format, chain P [auth A] mmCIF format, chain PB [auth C] mmCIF format, chain PC [auth D] mmCIF format, chain Q [auth A] mmCIF format, chain QB [auth C] mmCIF format, chain QC [auth D] mmCIF format, chain R [auth A] mmCIF format, chain RA [auth B] mmCIF format, chain RB [auth D] mmCIF format, chain S [auth A] mmCIF format, chain SA [auth B] mmCIF format, chain T [auth A] mmCIF format, chain TA [auth B] mmCIF format, chain TB [auth D] mmCIF format, chain UA [auth B] mmCIF format, chain VA [auth B] mmCIF format, chain W [auth A] mmCIF format, chain WA [auth B] mmCIF format, chain WB [auth D] mmCIF format, chain X [auth A] mmCIF format, chain XA [auth B] mmCIF format, chain XB [auth D] mmCIF format, chain Y [auth A] mmCIF format, chain YA [auth B] mmCIF format, chain YB [auth D] mmCIF format, chain Z [auth A] mmCIF format, chain ZA [auth C] mmCIF format, chain ZB [auth D]	AA [auth A] AB [auth C] AC [auth D] BA [auth A] BB [auth C] AA [auth A], AB [auth C], AC [auth D], BA [auth A], BB [auth C], BC [auth D], CC [auth D], DC [auth D], EB [auth C], EC [auth D], FA [auth B], FB [auth C], FC [auth D], G [auth A], GA [auth B], GB [auth C], GC [auth D], H [auth A], HA [auth B], HB [auth C], HC [auth D], I [auth A], IA [auth B], IB [auth C], IC [auth D], J [auth A], K [auth A], KA [auth B], L [auth A], LA [auth B], LB [auth C], M [auth A], MA [auth B], MC [auth D], NA [auth B], NC [auth D], O [auth A], OB [auth C], OC [auth D], P [auth A], PB [auth C], PC [auth D], Q [auth A], QB [auth C], QC [auth D], R [auth A], RA [auth B], RB [auth D], S [auth A], SA [auth B], T [auth A], TA [auth B], TB [auth D], UA [auth B], VA [auth B], W [auth A], WA [auth B], WB [auth D], X [auth A], XA [auth B], XB [auth D], Y [auth A], YA [auth B], YB [auth D], Z [auth A], ZA [auth C], ZB [auth D]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain AA [auth A] Focus chain AB [auth C] Focus chain AC [auth D] Focus chain BA [auth A] Focus chain BB [auth C] Focus chain BC [auth D] Focus chain CC [auth D] Focus chain DC [auth D] Focus chain EB [auth C] Focus chain EC [auth D] Focus chain FA [auth B] Focus chain FB [auth C] Focus chain FC [auth D] Focus chain G [auth A] Focus chain GA [auth B] Focus chain GB [auth C] Focus chain GC [auth D] Focus chain H [auth A] Focus chain HA [auth B] Focus chain HB [auth C] Focus chain HC [auth D] Focus chain I [auth A] Focus chain IA [auth B] Focus chain IB [auth C] Focus chain IC [auth D] Focus chain J [auth A] Focus chain K [auth A] Focus chain KA [auth B] Focus chain L [auth A] Focus chain LA [auth B] Focus chain LB [auth C] Focus chain M [auth A] Focus chain MA [auth B] Focus chain MC [auth D] Focus chain NA [auth B] Focus chain NC [auth D] Focus chain O [auth A] Focus chain OB [auth C] Focus chain OC [auth D] Focus chain P [auth A] Focus chain PB [auth C] Focus chain PC [auth D] Focus chain Q [auth A] Focus chain QB [auth C] Focus chain QC [auth D] Focus chain R [auth A] Focus chain RA [auth B] Focus chain RB [auth D] Focus chain S [auth A] Focus chain SA [auth B] Focus chain T [auth A] Focus chain TA [auth B] Focus chain TB [auth D] Focus chain UA [auth B] Focus chain VA [auth B] Focus chain W [auth A] Focus chain WA [auth B] Focus chain WB [auth D] Focus chain X [auth A] Focus chain XA [auth B] Focus chain XB [auth D] Focus chain Y [auth A] Focus chain YA [auth B] Focus chain YB [auth D] Focus chain Z [auth A] Focus chain ZA [auth C] Focus chain ZB [auth D] Interactions & Density Focus chain AA [auth A] Focus chain AB [auth C] Focus chain AC [auth D] Focus chain BA [auth A] Focus chain BB [auth C] Focus chain BC [auth D] Focus chain CC [auth D] Focus chain DC [auth D] Focus chain EB [auth C] Focus chain EC [auth D] Focus chain FA [auth B] Focus chain FB [auth C] Focus chain FC [auth D] Focus chain G [auth A] Focus chain GA [auth B] Focus chain GB [auth C] Focus chain GC [auth D] Focus chain H [auth A] Focus chain HA [auth B] Focus chain HB [auth C] Focus chain HC [auth D] Focus chain I [auth A] Focus chain IA [auth B] Focus chain IB [auth C] Focus chain IC [auth D] Focus chain J [auth A] Focus chain K [auth A] Focus chain KA [auth B] Focus chain L [auth A] Focus chain LA [auth B] Focus chain LB [auth C] Focus chain M [auth A] Focus chain MA [auth B] Focus chain MC [auth D] Focus chain NA [auth B] Focus chain NC [auth D] Focus chain O [auth A] Focus chain OB [auth C] Focus chain OC [auth D] Focus chain P [auth A] Focus chain PB [auth C] Focus chain PC [auth D] Focus chain Q [auth A] Focus chain QB [auth C] Focus chain QC [auth D] Focus chain R [auth A] Focus chain RA [auth B] Focus chain RB [auth D] Focus chain S [auth A] Focus chain SA [auth B] Focus chain T [auth A] Focus chain TA [auth B] Focus chain TB [auth D] Focus chain UA [auth B] Focus chain VA [auth B] Focus chain W [auth A] Focus chain WA [auth B] Focus chain WB [auth D] Focus chain X [auth A] Focus chain XA [auth B] Focus chain XB [auth D] Focus chain Y [auth A] Focus chain YA [auth B] Focus chain YB [auth D] Focus chain Z [auth A] Focus chain ZA [auth C] Focus chain ZB [auth D]
NI Query on NI Download Ideal Coordinates CCD File SDF format, chain CA [auth A] SDF format, chain RC [auth D] MOL2 format, chain CA [auth A] MOL2 format, chain RC [auth D] mmCIF format, chain CA [auth A] mmCIF format, chain RC [auth D]	CA [auth A], RC [auth D]	NICKEL (II) ION Ni VEQPNABPJHWNSG-UHFFFAOYSA-N		Interactions Focus chain CA [auth A] Focus chain RC [auth D] Interactions & Density Focus chain CA [auth A] Focus chain RC [auth D]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain DB [auth C] SDF format, chain EA [auth B] SDF format, chain F [auth A] SDF format, chain VB [auth D] MOL2 format, chain DB [auth C] MOL2 format, chain EA [auth B] MOL2 format, chain F [auth A] MOL2 format, chain VB [auth D] mmCIF format, chain DB [auth C] mmCIF format, chain EA [auth B] mmCIF format, chain F [auth A] mmCIF format, chain VB [auth D]	DB [auth C], EA [auth B], F [auth A], VB [auth D]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain DB [auth C] Focus chain EA [auth B] Focus chain F [auth A] Focus chain VB [auth D] Interactions & Density Focus chain DB [auth C] Focus chain EA [auth B] Focus chain F [auth A] Focus chain VB [auth D]

Binding Affinity Annotations
ID	Source	Binding Affinity
D68	BindingDB: 6FET	Ki: 0.3 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.88 Å
R-Value Free: 0.199
R-Value Work: 0.171
R-Value Observed: 0.173
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 97.19	α = 90
b = 110.71	β = 90
c = 161.48	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
Aimless	data scaling
REFMAC	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2019-04-24

Deposition Author(s):

Singh, A.K.

Brown, D.G.

Revision History (Full details and data files)

Version 1.0: 2019-04-24
Type: Initial release
Version 1.1: 2024-05-08
Changes: Data collection, Database references, Derived calculations, Refinement description