5L72

PI3 kinase delta in complex with N-[6-(5-methanesulfonamido-6-methoxypyridin-3-yl)-1,3-dihydro-2-benzofuran-4-yl]-2-(morpholin-4-yl)acetamide

PDB DOI: https://doi.org/10.2210/pdb5L72/pdb

Classification: TRANSFERASE
Organism(s): Mus musculus
Expression System: Spodoptera frugiperda
Mutation(s): No

Deposited: 2016-06-01 Released: 2016-07-27
Deposition Author(s): Rowland, P.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.06 Å
R-Value Free: 0.277
R-Value Work: 0.172
R-Value Observed: 0.178

wwPDB Validation 3D Report Full Report

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

Literature

Evolution of a Novel, Orally Bioavailable Series of PI3K delta Inhibitors from an Inhaled Lead for the Treatment of Respiratory Disease.

Amour, A., Barton, N., Cooper, A.W., Inglis, G., Jamieson, C., Luscombe, C.N., Morrell, J., Peace, S., Perez, D., Rowland, P., Tame, C., Uddin, S., Vitulli, G., Wellaway, N.

(2016) J Med Chem 59: 7239-7251

PubMed: 27429068 Search on PubMed
DOI: https://doi.org/10.1021/acs.jmedchem.6b00799
Primary Citation of Related Structures:
5L72

PubMed Abstract:
A four-step process of high-quality modeling of existing data, deconstruction, identification of replacement cores, and an innovative synthetic regrowth strategy led to the rapid discovery of a novel oral series of PI3Kδ inhibitors with promising selectivity and excellent in vivo characteristics.

Organizational Affiliation

GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.

Macromolecule Content

Total Structure Weight: 108.28 kDa
Atom Count: 7,225
Modelled Residue Count: 858
Deposited Residue Count: 940
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	A	940	Mus musculus	Mutation(s): 0 Gene Names: Pik3cd EC: 2.7.1.137 (PDB Primary Data), 2.7.1.153 (PDB Primary Data)
UniProt
Find proteins for O35904 (Mus musculus) Explore O35904 Go to UniProtKB: O35904
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O35904
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
6PF Query on 6PF Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	N-[6-(5-methanesulfonamido-6-methoxypyridin-3-yl)-1,3-dihydro-2-benzofuran-4-yl]-2-(morpholin-4-yl)acetamide C₂₁ H₂₄ N₄ O₆ S BZDMXCRKVCKVEV-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 3.06 Å
R-Value Free: 0.277
R-Value Work: 0.172
R-Value Observed: 0.178
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 141.4	α = 90
b = 64.36	β = 102.88
c = 115.83	γ = 90

Software Package:

Software Name	Purpose
BUSTER	refinement
XDS	data reduction
Aimless	data scaling

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2016-07-27

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2016-07-27
Type: Initial release
Version 1.1: 2016-08-24
Changes: Database references
Version 1.2: 2021-09-29
Changes: Database references, Structure summary

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.