PDBsum entry 6y6t

Hydrolase

PDB id

6y6t

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Contents

			Protein chain

					641 a.a.

			Ligands

					NAG-NAG ×3


					ODW


					NAG

			Metals

					_NI


					_CA

			Waters ×247

PDB id:

6y6t

Links

Name:

Hydrolase

Title:

Mouse galactocerebrosidase complexed with galacto-noeurostegine gns at ph 4.6

Structure:

Galactocerebrosidase. Chain: a. Synonym: galcerase,galactocerebroside beta-galactosidase, galactosylceramidase,galactosylceramide beta-galactosidase. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: galc. Expressed in: homo sapiens. Expression_system_taxid: 9606

Resolution:

2.25Å

R-factor:

0.161

R-free:

0.198

Authors:

J.E.Deane,J.Mcloughlin

Key ref:

A.Viuff et al. (2021). The Bicyclic Form of galacto-Noeurostegine Is a Potent Inhibitor of β-Galactocerebrosidase. ACS Med Chem Lett, 12, 56-59. PubMed id: 33488964 DOI: 10.1021/acsmedchemlett.0c00377

Date:

27-Feb-20

Release date:

13-Jan-21

PROCHECK

	Headers

	References

Protein chain

P54818 (GALC_MOUSE) - Galactocerebrosidase from Mus musculus

Seq: Struc:

Seq: Struc:					684 a.a. 641 a.a.

Key:

PfamA domain

Secondary structure



		Enzyme reactions

Enzyme class:

E.C.3.2.1.46 - galactosylceramidase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

a beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine + H2O = an N-acylsphing-4-enine + D-galactose

beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine

H2O

N-acylsphing-4-enine

D-galactose
Bound ligand (Het Group name = NAG)
matches with 62.50% similarity

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1021/acsmedchemlett.0c00377	ACS Med Chem Lett 12:56-59 (2021)
PubMed id: 33488964

The Bicyclic Form of galacto-Noeurostegine Is a Potent Inhibitor of β-Galactocerebrosidase.
A.Viuff, S.Salamone, J.McLoughlin, J.E.Deane, H.H.Jensen.

ABSTRACT

Competitive inhibitors of galactocerebrosidase (GALC) could be candidates for pharmacological chaperone therapy of patients with Krabbe disease. The known and selective nortropane-type iminosugar galacto-noeurostegine has been found to competitively inhibit GALC with K_i = 7 μM at pH 4.6, which is 330-fold more potent than the analogous deoxynoeurostegine. It was shown through X-ray protein crystallography that galacto-noeurostegine binds to the active site of GALC in its bicyclic form.