3LY2

Catalytic Domain of Human Phosphodiesterase 4B in Complex with A Coumarin-Based Inhibitor

PDB DOI: https://doi.org/10.2210/pdb3LY2/pdb

Classification: HYDROLASE/HYDROLASE INHIBITOR
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2010-02-26 Released: 2010-04-28
Deposition Author(s): Shiau, A.K., Coyle, A.R., Hsien, J.H., Staszewski, L.M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.233
R-Value Work: 0.205

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Water-soluble PDE4 inhibitors for the treatment of dry eye.

Govek, S.P., Oshiro, G., Anzola, J.V., Beauregard, C., Chen, J., Coyle, A.R., Gamache, D.A., Hellberg, M.R., Hsien, J.N., Lerch, J.M., Liao, J.C., Malecha, J.W., Staszewski, L.M., Thomas, D.J., Yanni, J.M., Noble, S.A., Shiau, A.K.

(2010) Bioorg Med Chem Lett 20: 2928-2932

PubMed: 20378348 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2010.03.023
Primary Citation of Related Structures:
3LY2

PubMed Abstract:
PDE4 inhibitors have the potential to alleviate the symptoms and underlying inflammation associated with dry eye. Disclosed herein is the development of a novel series of water-soluble PDE4 inhibitors. Our studies led to the discovery of coumarin 18, which is effective in a rabbit model of dry eye and a tear secretion test in rats.

Organizational Affiliation

Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, United States. sgovek@san.rr.com

Macromolecule Content

Total Structure Weight: 332.44 kDa
Atom Count: 22,265
Modelled Residue Count: 2,672
Deposited Residue Count: 2,856
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 4B	A, B, C, D, E A, B, C, D, E, F, G, H	357	Homo sapiens	Mutation(s): 0 Gene Names: DPDE4, PDE4B EC: 3.1.4.17
UniProt & NIH Common Fund Data Resources
Find proteins for Q07343 (Homo sapiens) Explore Q07343 Go to UniProtKB: Q07343
PHAROS: Q07343 GTEx: ENSG00000184588
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q07343
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
Z72 Query on Z72 Download Ideal Coordinates CCD File SDF format, chain CA [auth G] SDF format, chain FA [auth H] SDF format, chain I [auth A] SDF format, chain M [auth B] SDF format, chain Q [auth C] SDF format, chain T [auth D] SDF format, chain W [auth E] SDF format, chain Z [auth F] MOL2 format, chain CA [auth G] MOL2 format, chain FA [auth H] MOL2 format, chain I [auth A] MOL2 format, chain M [auth B] MOL2 format, chain Q [auth C] MOL2 format, chain T [auth D] MOL2 format, chain W [auth E] MOL2 format, chain Z [auth F]	CA [auth G] FA [auth H] I [auth A] M [auth B] Q [auth C] CA [auth G], FA [auth H], I [auth A], M [auth B], Q [auth C], T [auth D], W [auth E], Z [auth F]	8-(cyclopentyloxy)-4-[(3,5-dichloropyridin-4-yl)amino]-7-methoxy-2H-chromen-2-one C₂₀ H₁₈ Cl₂ N₂ O₄ YUTTWVBLGONANE-UHFFFAOYSA-N		Interactions Focus chain CA [auth G] Focus chain FA [auth H] Focus chain I [auth A] Focus chain M [auth B] Focus chain Q [auth C] Focus chain T [auth D] Focus chain W [auth E] Focus chain Z [auth F] Interactions & Density Focus chain CA [auth G] Focus chain FA [auth H] Focus chain I [auth A] Focus chain M [auth B] Focus chain Q [auth C] Focus chain T [auth D] Focus chain W [auth E] Focus chain Z [auth F]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain L [auth A] SDF format, chain P [auth B] MOL2 format, chain L [auth A] MOL2 format, chain P [auth B]	L [auth A], P [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain L [auth A] Focus chain P [auth B] Interactions & Density Focus chain L [auth A] Focus chain P [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain AA [auth F] SDF format, chain DA [auth G] SDF format, chain GA [auth H] SDF format, chain J [auth A] SDF format, chain N [auth B] SDF format, chain R [auth C] SDF format, chain U [auth D] SDF format, chain X [auth E] MOL2 format, chain AA [auth F] MOL2 format, chain DA [auth G] MOL2 format, chain GA [auth H] MOL2 format, chain J [auth A] MOL2 format, chain N [auth B] MOL2 format, chain R [auth C] MOL2 format, chain U [auth D] MOL2 format, chain X [auth E]	AA [auth F] DA [auth G] GA [auth H] J [auth A] N [auth B] AA [auth F], DA [auth G], GA [auth H], J [auth A], N [auth B], R [auth C], U [auth D], X [auth E]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain AA [auth F] Focus chain DA [auth G] Focus chain GA [auth H] Focus chain J [auth A] Focus chain N [auth B] Focus chain R [auth C] Focus chain U [auth D] Focus chain X [auth E] Interactions & Density Focus chain AA [auth F] Focus chain DA [auth G] Focus chain GA [auth H] Focus chain J [auth A] Focus chain N [auth B] Focus chain R [auth C] Focus chain U [auth D] Focus chain X [auth E]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain BA [auth F] SDF format, chain EA [auth G] SDF format, chain HA [auth H] SDF format, chain K [auth A] SDF format, chain O [auth B] SDF format, chain S [auth C] SDF format, chain V [auth D] SDF format, chain Y [auth E] MOL2 format, chain BA [auth F] MOL2 format, chain EA [auth G] MOL2 format, chain HA [auth H] MOL2 format, chain K [auth A] MOL2 format, chain O [auth B] MOL2 format, chain S [auth C] MOL2 format, chain V [auth D] MOL2 format, chain Y [auth E]	BA [auth F] EA [auth G] HA [auth H] K [auth A] O [auth B] BA [auth F], EA [auth G], HA [auth H], K [auth A], O [auth B], S [auth C], V [auth D], Y [auth E]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain BA [auth F] Focus chain EA [auth G] Focus chain HA [auth H] Focus chain K [auth A] Focus chain O [auth B] Focus chain S [auth C] Focus chain V [auth D] Focus chain Y [auth E] Interactions & Density Focus chain BA [auth F] Focus chain EA [auth G] Focus chain HA [auth H] Focus chain K [auth A] Focus chain O [auth B] Focus chain S [auth C] Focus chain V [auth D] Focus chain Y [auth E]

Binding Affinity Annotations
ID	Source	Binding Affinity
Z72	BindingDB: 3LY2	IC50: 5 (nM) from 1 assay(s)
Z72	PDBBind: 3LY2	IC50: 5 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.233
R-Value Work: 0.205
Space Group: C 2 2 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 214.796	α = 90
b = 233.964	β = 90
c = 165.258	γ = 90

Software Package:

Software Name	Purpose
Blu-Ice	data collection
PHASER	phasing
CNX	refinement
DENZO	data reduction
SCALEPACK	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2010-04-28

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2010-04-28
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance
Version 1.2: 2023-09-06
Changes: Data collection, Database references, Derived calculations, Refinement description

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Deposit Data

Help and Resources

3LY2

Catalytic Domain of Human Phosphodiesterase 4B in Complex with A Coumarin-Based Inhibitor

Water-soluble PDE4 inhibitors for the treatment of dry eye.

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

Expand

Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)