6IBT

Crystal structure of human alpha-galactosidase A in complex with alpha-galactose configured cyclophellitol aziridine ME737

PDB DOI: https://doi.org/10.2210/pdb6IBT/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Cricetulus griseus
Mutation(s): No

Deposited: 2018-11-30 Released: 2019-10-09
Deposition Author(s): Rowland, R.J., Wu, L., Davies, G.J.
Funding Organization(s): Biotechnology and Biological Sciences Research Council

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.04 Å
R-Value Free: 0.260
R-Value Work: 0.195
R-Value Observed: 0.198

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 2.2 of the entry. See complete history.

Literature

Alpha-d-Gal-cyclophellitol cyclosulfamidate is a Michaelis complex analog that stabilizes therapeutic lysosomal alpha-galactosidase A in Fabry disease

Artola, M., Hedberg, C., Rowland, R.J., Wu, L., Raich, L., Ferraz, M.J., Kytidou, K., Marel, G.A., Codee, J.D.C., Rovira, C., Aerts, J.M.F.G., Davies, G.J., Overkleeft, H.S.

(2019) Chem Sci

DOI: https://doi.org/10.1039/C9SC03342D

Macromolecule Content

Total Structure Weight: 95.68 kDa
Atom Count: 6,839
Modelled Residue Count: 782
Deposited Residue Count: 796
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Alpha-galactosidase A	A, B	398	Homo sapiens	Mutation(s): 0 Gene Names: GLA EC: 3.2.1.22
UniProt & NIH Common Fund Data Resources
Find proteins for P06280 (Homo sapiens) Explore P06280 Go to UniProtKB: P06280
PHAROS: P06280 GTEx: ENSG00000102393
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P06280
Glycosylation
Glycosylation Sites: 3	Glycosylation Focus chain A Focus chain B	Go to GlyGen: P06280-1
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

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Entity ID: 2
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	C	3		N-Glycosylation	Interactions Focus chain C Interactions & Density Focus chain C
Glycosylation Resources
GlyTouCan: G15407YE GlyCosmos: G15407YE GlyGen: G15407YE

Entity ID: 3
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
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	D, E	4		N-Glycosylation	Interactions Focus chain D Focus chain E Interactions & Density Focus chain D Focus chain E
Glycosylation Resources
GlyTouCan: G81315DD GlyCosmos: G81315DD GlyGen: G81315DD

Entity ID: 4
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	F	2		N-Glycosylation	Interactions Focus chain F Interactions & Density Focus chain F
Glycosylation Resources
GlyTouCan: G42666HT GlyCosmos: G42666HT GlyGen: G42666HT

Small Molecules

Ligands 6 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NAG Query on NAG Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain Z [auth B] MOL2 format, chain G [auth A] MOL2 format, chain Z [auth B] mmCIF format, chain G [auth A] mmCIF format, chain Z [auth B]	G [auth A], Z [auth B]	2-acetamido-2-deoxy-beta-D-glucopyranose C₈ H₁₅ N O₆ OVRNDRQMDRJTHS-FMDGEEDCSA-N		Interactions Focus chain G [auth A] Focus chain Z [auth B] Interactions & Density Focus chain G [auth A] Focus chain Z [auth B]
H9T (Subject of Investigation/LOI) Query on H9T Download Ideal Coordinates CCD File SDF format, chain L [auth A] SDF format, chain X [auth B] MOL2 format, chain L [auth A] MOL2 format, chain X [auth B] mmCIF format, chain L [auth A] mmCIF format, chain X [auth B]	L [auth A], X [auth B]	(1~{S},2~{S},3~{S},4~{S},5~{R},6~{S})-5-(hydroxymethyl)-7-azabicyclo[4.1.0]heptane-2,3,4-triol C₇ H₁₃ N O₄ GPIFFOGPRPKRHS-CLYCCYFHSA-N		Interactions Focus chain L [auth A] Focus chain X [auth B] Interactions & Density Focus chain L [auth A] Focus chain X [auth B]
PEG Query on PEG Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain M [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain M [auth A] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain M [auth A]	I [auth A], J [auth A], M [auth A]	DI(HYDROXYETHYL)ETHER C₄ H₁₀ O₃ MTHSVFCYNBDYFN-UHFFFAOYSA-N		Interactions Focus chain I [auth A] Focus chain J [auth A] Focus chain M [auth A] Interactions & Density Focus chain I [auth A] Focus chain J [auth A] Focus chain M [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain AA [auth B] SDF format, chain BA [auth B] SDF format, chain N [auth A] SDF format, chain O [auth A] SDF format, chain P [auth A] MOL2 format, chain AA [auth B] MOL2 format, chain BA [auth B] MOL2 format, chain N [auth A] MOL2 format, chain O [auth A] MOL2 format, chain P [auth A] mmCIF format, chain AA [auth B] mmCIF format, chain BA [auth B] mmCIF format, chain N [auth A] mmCIF format, chain O [auth A] mmCIF format, chain P [auth A]	AA [auth B], BA [auth B], N [auth A], O [auth A], P [auth A]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain AA [auth B] Focus chain BA [auth B] Focus chain N [auth A] Focus chain O [auth A] Focus chain P [auth A] Interactions & Density Focus chain AA [auth B] Focus chain BA [auth B] Focus chain N [auth A] Focus chain O [auth A] Focus chain P [auth A]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain K [auth A] SDF format, chain T [auth B] SDF format, chain U [auth B] SDF format, chain V [auth B] SDF format, chain W [auth B] SDF format, chain Y [auth B] MOL2 format, chain H [auth A] MOL2 format, chain K [auth A] MOL2 format, chain T [auth B] MOL2 format, chain U [auth B] MOL2 format, chain V [auth B] MOL2 format, chain W [auth B] MOL2 format, chain Y [auth B] mmCIF format, chain H [auth A] mmCIF format, chain K [auth A] mmCIF format, chain T [auth B] mmCIF format, chain U [auth B] mmCIF format, chain V [auth B] mmCIF format, chain W [auth B] mmCIF format, chain Y [auth B]	H [auth A] K [auth A] T [auth B] U [auth B] V [auth B] H [auth A], K [auth A], T [auth B], U [auth B], V [auth B], W [auth B], Y [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Focus chain K [auth A] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain Y [auth B] Interactions & Density Focus chain H [auth A] Focus chain K [auth A] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain Y [auth B]
ACT Query on ACT Download Ideal Coordinates CCD File SDF format, chain CA [auth B] SDF format, chain DA [auth B] SDF format, chain EA [auth B] SDF format, chain Q [auth A] SDF format, chain R [auth A] SDF format, chain S [auth A] MOL2 format, chain CA [auth B] MOL2 format, chain DA [auth B] MOL2 format, chain EA [auth B] MOL2 format, chain Q [auth A] MOL2 format, chain R [auth A] MOL2 format, chain S [auth A] mmCIF format, chain CA [auth B] mmCIF format, chain DA [auth B] mmCIF format, chain EA [auth B] mmCIF format, chain Q [auth A] mmCIF format, chain R [auth A] mmCIF format, chain S [auth A]	CA [auth B] DA [auth B] EA [auth B] Q [auth A] R [auth A] CA [auth B], DA [auth B], EA [auth B], Q [auth A], R [auth A], S [auth A]	ACETATE ION C₂ H₃ O₂ QTBSBXVTEAMEQO-UHFFFAOYSA-M		Interactions Focus chain CA [auth B] Focus chain DA [auth B] Focus chain EA [auth B] Focus chain Q [auth A] Focus chain R [auth A] Focus chain S [auth A] Interactions & Density Focus chain CA [auth B] Focus chain DA [auth B] Focus chain EA [auth B] Focus chain Q [auth A] Focus chain R [auth A] Focus chain S [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.04 Å
R-Value Free: 0.260
R-Value Work: 0.195
R-Value Observed: 0.198
Space Group: P 3₂ 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 90.39	α = 90
b = 90.39	β = 90
c = 216.59	γ = 120

Software Package:

Software Name	Purpose
REFMAC	refinement
xia2	data reduction
Aimless	data scaling
MOLREP	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2019-10-09

Deposition Author(s):

Rowland, R.J.

Wu, L.

Davies, G.J.

Funding Organization	Location	Grant Number
Biotechnology and Biological Sciences Research Council	United Kingdom	--

Revision History (Full details and data files)

Version 1.0: 2019-10-09
Type: Initial release
Version 2.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Atomic model, Data collection, Derived calculations, Structure summary
Version 2.1: 2024-01-24
Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary
Version 2.2: 2024-11-06
Changes: Structure summary