Molecular Playground/Human Galactosamine-6-sulfatase

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One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].
One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].
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===Human Lysosomal Protective Protein Cathepsin A (PPCA)===
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===Human galactosamine-6-sulfatase (GALNS)===
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[[Image:PPCA.jpg|frame|Human Lysosomal Protective Protein Cathepsin A]]
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[[Image:GALNS.jpg|frame|Human N-acetyl-galactosamine-6-sulfatase]]
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The human protective protein cathepsin A forms a multi-enzyme complex with beta-galactosidase and neuraminidase in lysosomes. PPCA has so far two functions:a catalytic activity overlapping with that of Cathepsin A and a protective function towards lysosomal beta-galactosidase and neuraminidase. The stability and activity of the latter glycosidases depend on their interaction with PPCA [1].
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The human lysosomal galactosamine-6-sulfatase (E.C. 3.1.6.4), also known as N-acetylgalactosamine-6-sulfatase, removes sulfate groups from a terminal N-acetyl-galactose-6-sulfate (or galactose-6-sulfate) in mucopolysaccharides such as keratan sulfate and chondroitin-6-sulfate Defects in GALNS lead to accumulation of mucopolysaccharides, resulting in the development of the lysosomal storage disease mucopolysaccharidosis 4A, also known as Morquio A disease[1].
{{Clear}}
{{Clear}}
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<applet load='1ivy' size='[450,338]' frame='true' align='right'
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<applet load='4FDJ' size='[450,338]' frame='true' align='right'
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caption='Human Lysosomal Protective Protein Cathepsin A (1ivy)' scene=''User:Yadilette_Rivera-Colon/Sandbox1/Loadedfrompdb/4'/>
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caption='human lysosomal galactosamine-6-sulfatase (4FDJ)' scene=''User:Yadilette_Rivera-Colon/Sandbox1/Loadedfrompdb/4'/>
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=== PPCA Glycosylation sites ===
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=== GALNS active site ===
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PPCA, is synthesized as a 542 amino acid precursor with a molecular weight of 54kDa. and it dimerizes soon after synthesis. The sequence contains two glycosylation sites, Asn 117 and Asn 305. It also contains nine cysteines. The spinning protein (<scene name='User:Yadilette_Rivera-Colon/Sandbox1/Glycosylation_sites_ppca/1'>PPCA Glycosylation sites</scene> ) is human protective protein with the glycosylation sites represented in stick model colored by atom.
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Sulfatases require maturation of a side chain residue into a catalytic nucleophile. In GALNS, the polypeptide chain encodes a cysteine at residue 79 at the start of the motif CXPXRXXL. The formylglycine generating enzyme recognizes this motif and converts Cys79 into a formylglycine aldehyde[2]. Hydration of the aldehyde by a water molecule generates the gem diol nucleophile dihydroxyalanine, which ligates Ca2+ in the active site. The spinning protein is human human lysosomal galactosamine-6-sulfatase with GalNac in the <scene name='Molecular_Playground/Human_Galactosamine-6-sulfatase/Galns_active_site/1'>GALNS active site</scene> a represented by spheres.
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==Additional Resources==
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For additional information, see: [[Metabolic Disorders]]
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<br />
===References: ===
===References: ===
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[1] Jackman, H. L., Morris, P. W., Deddish, P. A., Skidgel, R. A. and Erdos, E. G. (1992) J. Biol. Chem. 267, 2872-2875
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[1]Muenzer, J. Neufeld, E.F. The Mucopolysaccharidoses: In The Metabolic Basis of Inherited Disease, 8th ed. McGraw-Hill: Medical Publishing Division, 2001; Vol. 3 p 3431-3452.
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[2] K. von Figura, V. Gieselmann, J. Jaeken in The Metabolic and Molecular Bases of Inherited Disease, Vol. III, 8th ed. (Ed.: C. R. Scriver), McGraw-Hill, New York, 1999, p. 3695
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Molecular Playground banner: Human lysosomal galactosamine-6-sulfatase

Current revision

One of the CBI Molecules being studied in the University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground.

Contents

Human galactosamine-6-sulfatase (GALNS)

Human N-acetyl-galactosamine-6-sulfatase
Human N-acetyl-galactosamine-6-sulfatase

The human lysosomal galactosamine-6-sulfatase (E.C. 3.1.6.4), also known as N-acetylgalactosamine-6-sulfatase, removes sulfate groups from a terminal N-acetyl-galactose-6-sulfate (or galactose-6-sulfate) in mucopolysaccharides such as keratan sulfate and chondroitin-6-sulfate Defects in GALNS lead to accumulation of mucopolysaccharides, resulting in the development of the lysosomal storage disease mucopolysaccharidosis 4A, also known as Morquio A disease[1].

human lysosomal galactosamine-6-sulfatase (4FDJ)

Drag the structure with the mouse to rotate

GALNS active site

Sulfatases require maturation of a side chain residue into a catalytic nucleophile. In GALNS, the polypeptide chain encodes a cysteine at residue 79 at the start of the motif CXPXRXXL. The formylglycine generating enzyme recognizes this motif and converts Cys79 into a formylglycine aldehyde[2]. Hydration of the aldehyde by a water molecule generates the gem diol nucleophile dihydroxyalanine, which ligates Ca2+ in the active site. The spinning protein is human human lysosomal galactosamine-6-sulfatase with GalNac in the a represented by spheres.

Additional Resources

For additional information, see: Metabolic Disorders

References:

[1]Muenzer, J. Neufeld, E.F. The Mucopolysaccharidoses: In The Metabolic Basis of Inherited Disease, 8th ed. McGraw-Hill: Medical Publishing Division, 2001; Vol. 3 p 3431-3452.

[2] K. von Figura, V. Gieselmann, J. Jaeken in The Metabolic and Molecular Bases of Inherited Disease, Vol. III, 8th ed. (Ed.: C. R. Scriver), McGraw-Hill, New York, 1999, p. 3695


Molecular Playground banner: Human lysosomal galactosamine-6-sulfatase

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