5M0S

Structure-based evolution of a hybrid steroid series of Autotaxin inhibitors

PDB DOI: https://doi.org/10.2210/pdb5M0S/pdb

Classification: HYDROLASE
Organism(s): Rattus norvegicus
Expression System: Homo sapiens
Mutation(s): Yes

Deposited: 2016-10-05 Released: 2017-08-16
Deposition Author(s): Keune, W.-J., Heidebrecht, T., Perrakis, A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Free: 0.286
R-Value Work: 0.238
R-Value Observed: 0.240

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 2.1 of the entry. See complete history.

Macromolecule Content

Total Structure Weight: 100.18 kDa
Atom Count: 6,592
Modelled Residue Count: 777
Deposited Residue Count: 827
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Ectonucleotide pyrophosphatase/phosphodiesterase family member 2	A	827	Rattus norvegicus	Mutation(s): 4 Gene Names: Enpp2, Atx, Npps2 EC: 3.1.4.39
UniProt
Find proteins for Q64610 (Rattus norvegicus) Explore Q64610 Go to UniProtKB: Q64610
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q64610
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

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Entity ID: 2
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	B	9		N-Glycosylation	Interactions Focus chain B Interactions & Density Focus chain B
Glycosylation Resources
GlyTouCan: G37135JQ GlyCosmos: G37135JQ GlyGen: G37135JQ

Small Molecules

Ligands 7 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
7CW Query on 7CW Download Ideal Coordinates CCD File SDF format, chain R [auth A] MOL2 format, chain R [auth A]	R [auth A]	[3,5-bis(chloranyl)phenyl]methyl ~{N}-[2-[[(4~{R})-4-[(3~{R},5~{S},7~{S},8~{R},9~{S},10~{S},13~{R},14~{S},17~{R})-10,13-dimethyl-3,7-bis(oxidanyl)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1~{H}-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethyl]carbamate C₃₄ H₅₀ Cl₂ N₂ O₅ RGSSNYYHNQIMAB-ZSCMZCBDSA-N		Interactions Focus chain R [auth A] Interactions & Density Focus chain R [auth A]
IOD Query on IOD Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain J [auth A] SDF format, chain JA [auth A] SDF format, chain L [auth A] SDF format, chain O [auth A] SDF format, chain P [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain K [auth A] SDF format, chain M [auth A] SDF format, chain N [auth A] SDF format, chain Q [auth A] MOL2 format, chain F [auth A] MOL2 format, chain J [auth A] MOL2 format, chain JA [auth A] MOL2 format, chain L [auth A] MOL2 format, chain O [auth A] MOL2 format, chain P [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain K [auth A] MOL2 format, chain M [auth A] MOL2 format, chain N [auth A] MOL2 format, chain Q [auth A]	F [auth A] G [auth A] H [auth A] I [auth A] J [auth A] F [auth A], G [auth A], H [auth A], I [auth A], J [auth A], JA [auth A], K [auth A], L [auth A], M [auth A], N [auth A], O [auth A], P [auth A], Q [auth A]	IODIDE ION I XMBWDFGMSWQBCA-UHFFFAOYSA-M		Interactions Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain JA [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain P [auth A] Focus chain Q [auth A] Interactions & Density Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain JA [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain P [auth A] Focus chain Q [auth A]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain EA [auth A] SDF format, chain GA [auth A] SDF format, chain HA [auth A] SDF format, chain IA [auth A] SDF format, chain FA [auth A] MOL2 format, chain EA [auth A] MOL2 format, chain GA [auth A] MOL2 format, chain HA [auth A] MOL2 format, chain IA [auth A] MOL2 format, chain FA [auth A]	EA [auth A], FA [auth A], GA [auth A], HA [auth A], IA [auth A]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain EA [auth A] Focus chain FA [auth A] Focus chain GA [auth A] Focus chain HA [auth A] Focus chain IA [auth A] Interactions & Density Focus chain EA [auth A] Focus chain FA [auth A] Focus chain GA [auth A] Focus chain HA [auth A] Focus chain IA [auth A]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain D [auth A]	D [auth A], E [auth A]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Interactions & Density Focus chain D [auth A] Focus chain E [auth A]
SCN Query on SCN Download Ideal Coordinates CCD File SDF format, chain AA [auth A] SDF format, chain BA [auth A] SDF format, chain DA [auth A] SDF format, chain U [auth A] SDF format, chain V [auth A] SDF format, chain W [auth A] SDF format, chain CA [auth A] SDF format, chain T [auth A] SDF format, chain X [auth A] SDF format, chain Y [auth A] SDF format, chain Z [auth A] MOL2 format, chain AA [auth A] MOL2 format, chain BA [auth A] MOL2 format, chain DA [auth A] MOL2 format, chain U [auth A] MOL2 format, chain V [auth A] MOL2 format, chain W [auth A] MOL2 format, chain CA [auth A] MOL2 format, chain T [auth A] MOL2 format, chain X [auth A] MOL2 format, chain Y [auth A] MOL2 format, chain Z [auth A]	AA [auth A] BA [auth A] CA [auth A] DA [auth A] T [auth A] AA [auth A], BA [auth A], CA [auth A], DA [auth A], T [auth A], U [auth A], V [auth A], W [auth A], X [auth A], Y [auth A], Z [auth A]	THIOCYANATE ION C N S ZMZDMBWJUHKJPS-UHFFFAOYSA-M		Interactions Focus chain AA [auth A] Focus chain BA [auth A] Focus chain CA [auth A] Focus chain DA [auth A] Focus chain T [auth A] Focus chain U [auth A] Focus chain V [auth A] Focus chain W [auth A] Focus chain X [auth A] Focus chain Y [auth A] Focus chain Z [auth A] Interactions & Density Focus chain AA [auth A] Focus chain BA [auth A] Focus chain CA [auth A] Focus chain DA [auth A] Focus chain T [auth A] Focus chain U [auth A] Focus chain V [auth A] Focus chain W [auth A] Focus chain X [auth A] Focus chain Y [auth A] Focus chain Z [auth A]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A]	C [auth A]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
NA Query on NA Download Ideal Coordinates CCD File SDF format, chain S [auth A] MOL2 format, chain S [auth A]	S [auth A]	SODIUM ION Na FKNQFGJONOIPTF-UHFFFAOYSA-N		Interactions Focus chain S [auth A] Interactions & Density Focus chain S [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
7CW	BindingDB: 5M0S	IC50: 202 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Free: 0.286
R-Value Work: 0.238
R-Value Observed: 0.240
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 62.826	α = 90
b = 88.857	β = 103.08
c = 77.293	γ = 90

Software Package:

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

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2017-08-16

Deposition Author(s):

Keune, W.-J.

Heidebrecht, T.

Perrakis, A.

Revision History (Full details and data files)

Version 1.0: 2017-08-16
Type: Initial release
Version 1.1: 2019-10-16
Changes: Data collection
Version 2.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Atomic model, Data collection, Derived calculations, Structure summary
Version 2.1: 2024-01-17
Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary