6FW3

Crystal structure of human phosphodiesterase 4D2 catalytic domain with inhibitor NPD-007

PDB DOI: https://doi.org/10.2210/pdb6FW3/pdb

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

Deposited: 2018-03-05 Released: 2019-03-20
Deposition Author(s): Singh, A.K., Brown, D.G.
Funding Organization(s): European Union

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.78 Å
R-Value Free: 0.214
R-Value Work: 0.177
R-Value Observed: 0.179

Starting Model: experimental
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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-007

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: 174.89 kDa
Atom Count: 11,966
Modelled Residue Count: 1,302
Deposited Residue Count: 1,456
Unique protein chains: 1

Macromolecules

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(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 7 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
E8H (Subject of Investigation/LOI) Query on E8H Download Ideal Coordinates CCD File SDF format, chain AA [auth A] SDF format, chain EC [auth D] SDF format, chain LB [auth C] SDF format, chain TA [auth B] MOL2 format, chain AA [auth A] MOL2 format, chain EC [auth D] MOL2 format, chain LB [auth C] MOL2 format, chain TA [auth B] mmCIF format, chain AA [auth A] mmCIF format, chain EC [auth D] mmCIF format, chain LB [auth C] mmCIF format, chain TA [auth B]	AA [auth A], EC [auth D], LB [auth C], TA [auth B]	1-(2-{4-[(4aS,8aR)-4-(3,4-dimethoxyphenyl)-1-oxo-1,2,4a,5,8,8a-hexahydrophthalazin-2-yl]piperidin-1-yl}-2-oxoethyl)pyrrolidine-2,5-dione C₂₇ H₃₂ N₄ O₆ BLRZNXZBGGTDMQ-VQTJNVASSA-N		Interactions Focus chain AA [auth A] Focus chain EC [auth D] Focus chain LB [auth C] Focus chain TA [auth B] Interactions & Density Focus chain AA [auth A] Focus chain EC [auth D] Focus chain LB [auth C] Focus chain TA [auth B]
EPE Query on EPE Download Ideal Coordinates CCD File SDF format, chain CC [auth D] SDF format, chain EB [auth C] SDF format, chain JA [auth B] SDF format, chain OA [auth B] SDF format, chain Y [auth A] MOL2 format, chain CC [auth D] MOL2 format, chain EB [auth C] MOL2 format, chain JA [auth B] MOL2 format, chain OA [auth B] MOL2 format, chain Y [auth A] mmCIF format, chain CC [auth D] mmCIF format, chain EB [auth C] mmCIF format, chain JA [auth B] mmCIF format, chain OA [auth B] mmCIF format, chain Y [auth A]	CC [auth D], EB [auth C], JA [auth B], OA [auth B], Y [auth A]	4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID C₈ H₁₈ N₂ O₄ S JKMHFZQWWAIEOD-UHFFFAOYSA-N		Interactions Focus chain CC [auth D] Focus chain EB [auth C] Focus chain JA [auth B] Focus chain OA [auth B] Focus chain Y [auth A] Interactions & Density Focus chain CC [auth D] Focus chain EB [auth C] Focus chain JA [auth B] Focus chain OA [auth B] Focus chain Y [auth A]
PG4 Query on PG4 Download Ideal Coordinates CCD File SDF format, chain MB [auth C] MOL2 format, chain MB [auth C] mmCIF format, chain MB [auth C]	MB [auth C]	TETRAETHYLENE GLYCOL C₈ H₁₈ O₅ UWHCKJMYHZGTIT-UHFFFAOYSA-N		Interactions Focus chain MB [auth C] Interactions & Density Focus chain MB [auth C]
PEG Query on PEG Download Ideal Coordinates CCD File SDF format, chain O [auth A] SDF format, chain VB [auth D] MOL2 format, chain O [auth A] MOL2 format, chain VB [auth D] mmCIF format, chain O [auth A] mmCIF format, chain VB [auth D]	O [auth A], VB [auth D]	DI(HYDROXYETHYL)ETHER C₄ H₁₀ O₃ MTHSVFCYNBDYFN-UHFFFAOYSA-N		Interactions Focus chain O [auth A] Focus chain VB [auth D] Interactions & Density Focus chain O [auth A] Focus chain VB [auth D]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain DA [auth B] SDF format, chain E [auth A] SDF format, chain PB [auth D] SDF format, chain WA [auth C] MOL2 format, chain DA [auth B] MOL2 format, chain E [auth A] MOL2 format, chain PB [auth D] MOL2 format, chain WA [auth C] mmCIF format, chain DA [auth B] mmCIF format, chain E [auth A] mmCIF format, chain PB [auth D] mmCIF format, chain WA [auth C]	DA [auth B], E [auth A], PB [auth D], WA [auth C]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain DA [auth B] Focus chain E [auth A] Focus chain PB [auth D] Focus chain WA [auth C] Interactions & Density Focus chain DA [auth B] Focus chain E [auth A] Focus chain PB [auth D] Focus chain WA [auth C]
EDO Query on EDO Download Ideal Coordinates CCD File 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 CA [auth A] SDF format, chain CB [auth C] SDF format, chain DB [auth C] SDF format, chain DC [auth D] SDF format, chain FA [auth B] SDF format, chain FB [auth C] SDF format, chain G [auth A] SDF format, chain GA [auth B] SDF format, chain GB [auth C] SDF format, chain H [auth A] SDF format, chain HA [auth B] SDF format, chain HB [auth C] SDF format, chain I [auth A] SDF format, chain IA [auth B] SDF format, chain IB [auth C] SDF format, chain J [auth A] SDF format, chain JB [auth C] SDF format, chain K [auth A] SDF format, chain KA [auth B] SDF format, chain KB [auth C] SDF format, chain L [auth A] SDF format, chain LA [auth B] SDF format, chain M [auth A] SDF format, chain MA [auth B] SDF format, chain N [auth A] SDF format, chain NA [auth B] SDF format, chain NB [auth D] SDF format, chain OB [auth D] SDF format, chain P [auth A] SDF format, chain PA [auth B] SDF format, chain Q [auth A] SDF format, chain QA [auth B] 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 SB [auth D] SDF format, chain T [auth A] SDF format, chain TB [auth D] SDF format, chain U [auth A] SDF format, chain UA [auth C] SDF format, chain UB [auth D] SDF format, chain V [auth A] SDF format, chain VA [auth C] SDF format, chain W [auth A] SDF format, chain WB [auth D] SDF format, chain X [auth A] SDF format, chain XB [auth D] SDF format, chain YA [auth C] 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 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 CA [auth A] MOL2 format, chain CB [auth C] MOL2 format, chain DB [auth C] MOL2 format, chain DC [auth D] MOL2 format, chain FA [auth B] MOL2 format, chain FB [auth C] MOL2 format, chain G [auth A] MOL2 format, chain GA [auth B] MOL2 format, chain GB [auth C] MOL2 format, chain H [auth A] MOL2 format, chain HA [auth B] MOL2 format, chain HB [auth C] MOL2 format, chain I [auth A] MOL2 format, chain IA [auth B] MOL2 format, chain IB [auth C] MOL2 format, chain J [auth A] MOL2 format, chain JB [auth C] MOL2 format, chain K [auth A] MOL2 format, chain KA [auth B] MOL2 format, chain KB [auth C] MOL2 format, chain L [auth A] MOL2 format, chain LA [auth B] MOL2 format, chain M [auth A] MOL2 format, chain MA [auth B] MOL2 format, chain N [auth A] MOL2 format, chain NA [auth B] MOL2 format, chain NB [auth D] MOL2 format, chain OB [auth D] MOL2 format, chain P [auth A] MOL2 format, chain PA [auth B] MOL2 format, chain Q [auth A] MOL2 format, chain QA [auth B] 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 SB [auth D] MOL2 format, chain T [auth A] MOL2 format, chain TB [auth D] MOL2 format, chain U [auth A] MOL2 format, chain UA [auth C] MOL2 format, chain UB [auth D] MOL2 format, chain V [auth A] MOL2 format, chain VA [auth C] MOL2 format, chain W [auth A] MOL2 format, chain WB [auth D] MOL2 format, chain X [auth A] MOL2 format, chain XB [auth D] MOL2 format, chain YA [auth C] 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 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 CA [auth A] mmCIF format, chain CB [auth C] mmCIF format, chain DB [auth C] mmCIF format, chain DC [auth D] mmCIF format, chain FA [auth B] mmCIF format, chain FB [auth C] mmCIF format, chain G [auth A] mmCIF format, chain GA [auth B] mmCIF format, chain GB [auth C] mmCIF format, chain H [auth A] mmCIF format, chain HA [auth B] mmCIF format, chain HB [auth C] mmCIF format, chain I [auth A] mmCIF format, chain IA [auth B] mmCIF format, chain IB [auth C] mmCIF format, chain J [auth A] mmCIF format, chain JB [auth C] mmCIF format, chain K [auth A] mmCIF format, chain KA [auth B] mmCIF format, chain KB [auth C] mmCIF format, chain L [auth A] mmCIF format, chain LA [auth B] mmCIF format, chain M [auth A] mmCIF format, chain MA [auth B] mmCIF format, chain N [auth A] mmCIF format, chain NA [auth B] mmCIF format, chain NB [auth D] mmCIF format, chain OB [auth D] mmCIF format, chain P [auth A] mmCIF format, chain PA [auth B] mmCIF format, chain Q [auth A] mmCIF format, chain QA [auth B] 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 SB [auth D] mmCIF format, chain T [auth A] mmCIF format, chain TB [auth D] mmCIF format, chain U [auth A] mmCIF format, chain UA [auth C] mmCIF format, chain UB [auth D] mmCIF format, chain V [auth A] mmCIF format, chain VA [auth C] mmCIF format, chain W [auth A] mmCIF format, chain WB [auth D] mmCIF format, chain X [auth A] mmCIF format, chain XB [auth D] mmCIF format, chain YA [auth C] mmCIF format, chain YB [auth D] mmCIF format, chain Z [auth A] mmCIF format, chain ZA [auth C] mmCIF format, chain ZB [auth D]	AB [auth C] AC [auth D] BA [auth A] BB [auth C] BC [auth D] AB [auth C], AC [auth D], BA [auth A], BB [auth C], BC [auth D], CA [auth A], CB [auth C], DB [auth C], DC [auth D], FA [auth B], FB [auth C], G [auth A], GA [auth B], GB [auth C], H [auth A], HA [auth B], HB [auth C], I [auth A], IA [auth B], IB [auth C], J [auth A], JB [auth C], K [auth A], KA [auth B], KB [auth C], L [auth A], LA [auth B], M [auth A], MA [auth B], N [auth A], NA [auth B], NB [auth D], OB [auth D], P [auth A], PA [auth B], Q [auth A], QA [auth B], R [auth A], RA [auth B], RB [auth D], S [auth A], SA [auth B], SB [auth D], T [auth A], TB [auth D], U [auth A], UA [auth C], UB [auth D], V [auth A], VA [auth C], W [auth A], WB [auth D], X [auth A], XB [auth D], YA [auth C], YB [auth D], Z [auth A], ZA [auth C], ZB [auth D]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions 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 CA [auth A] Focus chain CB [auth C] Focus chain DB [auth C] Focus chain DC [auth D] Focus chain FA [auth B] Focus chain FB [auth C] Focus chain G [auth A] Focus chain GA [auth B] Focus chain GB [auth C] Focus chain H [auth A] Focus chain HA [auth B] Focus chain HB [auth C] Focus chain I [auth A] Focus chain IA [auth B] Focus chain IB [auth C] Focus chain J [auth A] Focus chain JB [auth C] Focus chain K [auth A] Focus chain KA [auth B] Focus chain KB [auth C] Focus chain L [auth A] Focus chain LA [auth B] Focus chain M [auth A] Focus chain MA [auth B] Focus chain N [auth A] Focus chain NA [auth B] Focus chain NB [auth D] Focus chain OB [auth D] Focus chain P [auth A] Focus chain PA [auth B] Focus chain Q [auth A] Focus chain QA [auth B] 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 SB [auth D] Focus chain T [auth A] Focus chain TB [auth D] Focus chain U [auth A] Focus chain UA [auth C] Focus chain UB [auth D] Focus chain V [auth A] Focus chain VA [auth C] Focus chain W [auth A] Focus chain WB [auth D] Focus chain X [auth A] Focus chain XB [auth D] Focus chain YA [auth C] Focus chain YB [auth D] Focus chain Z [auth A] Focus chain ZA [auth C] Focus chain ZB [auth D] Interactions & Density 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 CA [auth A] Focus chain CB [auth C] Focus chain DB [auth C] Focus chain DC [auth D] Focus chain FA [auth B] Focus chain FB [auth C] Focus chain G [auth A] Focus chain GA [auth B] Focus chain GB [auth C] Focus chain H [auth A] Focus chain HA [auth B] Focus chain HB [auth C] Focus chain I [auth A] Focus chain IA [auth B] Focus chain IB [auth C] Focus chain J [auth A] Focus chain JB [auth C] Focus chain K [auth A] Focus chain KA [auth B] Focus chain KB [auth C] Focus chain L [auth A] Focus chain LA [auth B] Focus chain M [auth A] Focus chain MA [auth B] Focus chain N [auth A] Focus chain NA [auth B] Focus chain NB [auth D] Focus chain OB [auth D] Focus chain P [auth A] Focus chain PA [auth B] Focus chain Q [auth A] Focus chain QA [auth B] 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 SB [auth D] Focus chain T [auth A] Focus chain TB [auth D] Focus chain U [auth A] Focus chain UA [auth C] Focus chain UB [auth D] Focus chain V [auth A] Focus chain VA [auth C] Focus chain W [auth A] Focus chain WB [auth D] Focus chain X [auth A] Focus chain XB [auth D] Focus chain YA [auth C] Focus chain YB [auth D] Focus chain Z [auth A] Focus chain ZA [auth C] Focus chain ZB [auth D]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain EA [auth B] SDF format, chain F [auth A] SDF format, chain QB [auth D] SDF format, chain XA [auth C] MOL2 format, chain EA [auth B] MOL2 format, chain F [auth A] MOL2 format, chain QB [auth D] MOL2 format, chain XA [auth C] mmCIF format, chain EA [auth B] mmCIF format, chain F [auth A] mmCIF format, chain QB [auth D] mmCIF format, chain XA [auth C]	EA [auth B], F [auth A], QB [auth D], XA [auth C]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain EA [auth B] Focus chain F [auth A] Focus chain QB [auth D] Focus chain XA [auth C] Interactions & Density Focus chain EA [auth B] Focus chain F [auth A] Focus chain QB [auth D] Focus chain XA [auth C]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.78 Å
R-Value Free: 0.214
R-Value Work: 0.177
R-Value Observed: 0.179
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 99.11	α = 90
b = 110.717	β = 90
c = 161.49	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
Aimless	data scaling
PHASER	phasing
DIALS	data collection

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2019-03-20

Deposition Author(s):

Singh, A.K.

Brown, D.G.

Funding Organization	Location	Grant Number
European Union		602666

Revision History (Full details and data files)

Version 1.0: 2019-03-20
Type: Initial release
Version 1.1: 2024-01-17
Changes: Data collection, Database references, Derived calculations, Refinement description