2x0y

From Proteopedia

Screening-based discovery of drug-like O-GlcNAcase inhibitor scaffolds

Structural highlights

2x0y is a 2 chain structure with sequence from Clostridium perfringens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.25Å
Ligands:	X0T
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

OGA_CLOP1 Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins.

Evolutionary Conservation

Checkto colour the structure by Evolutionary Conservation, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

O-GlcNAcylation is an essential posttranslational modification in metazoa. Modulation of O-GlcNAc levels with small molecule inhibitors of O-GlcNAc hydrolase (OGA) is a useful strategy to probe the role of this modification in a range of cellular processes. Here we report the discovery of novel, low molecular weight and drug-like O-GlcNAcase inhibitor scaffolds by high-throughput screening. Kinetic and X-ray crystallographic analyses of the binding modes with human/bacterial O-GlcNAcases identify some of these as competitive inhibitors. Comparative kinetic experiments with the mechanistically related human lysosomal hexosaminidases reveal that three of the inhibitor scaffolds show selectivity towards human OGA. These scaffolds provide attractive starting points for the development of non-carbohydrate, drug-like OGA inhibitors.

Screening-based discovery of drug-like O-GlcNAcase inhibitor scaffolds.,Dorfmueller HC, van Aalten DM FEBS Lett. 2010 Feb 19;584(4):694-700. Epub 2009 Dec 16. PMID:20026047^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations

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References

↑ Dorfmueller HC, van Aalten DM. Screening-based discovery of drug-like O-GlcNAcase inhibitor scaffolds. FEBS Lett. 2010 Feb 19;584(4):694-700. Epub 2009 Dec 16. PMID:20026047 doi:10.1016/j.febslet.2009.12.020

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

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PDB ID 2x0y

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Categories: Clostridium perfringens | Large Structures | Dorfmueller HC | Van Aalten DMF

2x0y

From Proteopedia

Screening-based discovery of drug-like O-GlcNAcase inhibitor scaffolds

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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