4V24

Sphingosine kinase 1 in complex with PF-543

PDB DOI: https://doi.org/10.2210/pdb4V24/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): No

Deposited: 2014-10-05 Released: 2014-10-15
Deposition Author(s): Elkins, J.M., Wang, J., Sorrell, F., Tallant, C., Wang, D., Shrestha, L., Bountra, C., von Delft, F., Knapp, S., Edwards, A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free: 0.210
R-Value Work: 0.182
R-Value Observed: 0.183

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Crystal Structure of Sphingosine Kinase 1 with Pf-543.

Wang, J., Knapp, S., Pyne, N.J., Pyne, S., Elkins, J.M.

(2014) ACS Med Chem Lett 5: 1329

PubMed: 25516793 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1021/ml5004074
Primary Citation of Related Structures:
4V24

PubMed Abstract:
The most potent inhibitor of Sphingosine Kinase 1 (SPHK1) so far identified is PF-543. The crystal structure of SPHK1 in complex with inhibitor PF-543 to 1.8 Å resolution reveals the inhibitor bound in a bent conformation analogous to that expected of a bound sphingosine substrate but with a rotated head group. The structural data presented will aid in the design of SPHK1 and SPHK2 inhibitors with improved properties.

Organizational Affiliation

Structural Genomics Consortium, University of Oxford , Old Road Campus Research Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, U.K.

Macromolecule Content

Total Structure Weight: 83.33 kDa
Atom Count: 6,004
Modelled Residue Count: 700
Deposited Residue Count: 742
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
SPHINGOSINE KINASE 1	A, B	371	Homo sapiens	Mutation(s): 0 EC: 2.7.1.91
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NYA1 (Homo sapiens) Explore Q9NYA1 Go to UniProtKB: Q9NYA1
PHAROS: Q9NYA1 GTEx: ENSG00000176170
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9NYA1
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
GYR Query on GYR Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain E [auth B] MOL2 format, chain C [auth A] MOL2 format, chain E [auth B]	C [auth A], E [auth B]	{(2R)-1-[4-({3-METHYL-5-[(PHENYLSULFONYL)METHYL]PHENOXY}METHYL)BENZYL]PYRROLIDIN-2-YL}METHANOL C₂₇ H₃₁ N O₄ S NPUXORBZRBIOMQ-RUZDIDTESA-N		Interactions Focus chain C [auth A] Focus chain E [auth B] Interactions & Density Focus chain C [auth A] Focus chain E [auth B]
ACT Query on ACT Download Ideal Coordinates CCD File SDF format, chain D [auth A] MOL2 format, chain D [auth A]	D [auth A]	ACETATE ION C₂ H₃ O₂ QTBSBXVTEAMEQO-UHFFFAOYSA-M		Interactions Focus chain D [auth A] Interactions & Density Focus chain D [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
GYR	Binding MOAD: 4V24	Ki: 4.3 (nM) from 1 assay(s)
	BindingDB: 4V24	Ki: min: 3.6, max: 4.3 (nM) from 3 assay(s)
		Kd: 5 (nM) from 1 assay(s)
		IC50: min: 0.8, max: 387 (nM) from 8 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free: 0.210
R-Value Work: 0.182
R-Value Observed: 0.183
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 86.57	α = 90
b = 60.549	β = 107.17
c = 89.592	γ = 90

Software Package:

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

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2014-10-15

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2014-10-15
Type: Initial release
Version 1.1: 2014-12-31
Changes: Database references
Version 1.2: 2018-01-24
Changes: Structure summary
Version 1.3: 2024-01-10
Changes: Data collection, Database references, Derived calculations, Other, Refinement description