Proteopedia - User contributions [en]

Galactosylceramidase

2014-06-06T18:52:11Z

Alison Stivers:

<StructureSection load='3zr6' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a [[hydrolase]] <ref name=PDB>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr6 3ZR6]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galc_galactose/2'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa monomer consisting of a 656 residues, which form a <scene name='58/587874/Galc_galactose_sec/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref name=PDB>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>. The TIM barrel is composed of eight parallel β-strands surrounded by α-helices and a single disulfide bridge between residues Cys 271 and Cys 378, while the β-sandwich is composed of two twisted β-sheets. The lectin domain is characterized by a calcium ion that is bound in pentagonal bipyramidal configuration<ref name=Deane>PMID: 21876145</ref>.

The substrate-binding site of GALC is mostly comprised of the central TIM barrel, however loops from the other two domains also appear to contribute to the binding pocket. Residues that appear to interact with the substrate by hydrogen bonding include Gly48, Thr93, Trp135, Asn181, Glu182, Glu258, Ser261, and Arg380. Of particular interest are the residues Glu258 and Glu182, which have been proposed as the active site nucleophile and proton donor respectively, due to the average distance between the carboxyl oxygens being consistent with the retaining mechanism of glycosidic bond hydrolysis.<ref name=Deane>PMID: 21876145</ref>

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Because Krabbe disease is caused by a ''decrease'' in galactosylceramidase activity, there are no drug-protein interactions to explore. However some natural inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="()"}
- Twelve.
+ Forty-One.
- Sixty.

{What class of protein is galactosylceramidase?
|type="()"}
+ Hydrolase.
- Isomerase.
- Ligase.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-06T18:48:31Z

Alison Stivers:

<StructureSection load='3zr6' size='340' side='right' caption='Galactosylceramidase scene=''>

'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a [[hydrolase]] <ref name=PDB>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr6 3ZR6]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galc_galactose/2'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa monomer consisting of a 656 residues, which form a <scene name='58/587874/Galc_galactose_sec/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref name=PDB>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>. The TIM barrel is composed of eight parallel β-strands surrounded by α-helices and a single disulfide bridge between residues Cys 271 and Cys 378, while the β-sandwich is composed of two twisted β-sheets. The lectin domain is characterized by a calcium ion that is bound in pentagonal bipyramidal configuration<ref name=Deane>PMID: 21876145</ref>.

The substrate-binding site of GALC is mostly comprised of the central TIM barrel, however loops from the other two domains also appear to contribute to the binding pocket. Residues that appear to interact with the substrate by hydrogen bonding include Gly48, Thr93, Trp135, Asn181, Glu182, Glu258, Ser261, and Arg380. Of particular interest are the residues Glu258 and Glu182, which have been proposed as the active site nucleophile and proton donor respectively, due to the average distance between the carboxyl oxygens being consistent with the retaining mechanism of glycosidic bond hydrolysis.<ref name=Deane>PMID: 21876145</ref>

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Because Krabbe disease is caused by a ''decrease'' in galactosylceramidase activity, there are no drug-protein interactions to explore. However some natural inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="()"}
- Twelve.
+ Forty-One.
- Sixty.

{What class of protein is galactosylceramidase?
|type="()"}
+ Hydrolase.
- Isomerase.
- Ligase.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-05T18:08:30Z

Alison Stivers:

<StructureSection load='3zr6' size='340' side='right' caption='Galactosylceramidase scene=''>

'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a [[hydrolase]] <ref name=PDB>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr6 3ZR6]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa monomer consisting of a 656 residues, which form a <scene name='58/587874/Galactosylceramidase_secondary/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref name=PDB>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>. The TIM barrel is composed of eight parallel β-strands surrounded by α-helices and a single disulfide bridge between residues Cys 271 and Cys 378, while the β-sandwich is composed of two twisted β-sheets. The lectin domain is characterized by a calcium ion that is bound in pentagonal bipyramidal configuration<ref name=Deane>PMID: 21876145</ref>.

The substrate-binding site of GALC is mostly comprised of the central TIM barrel, however loops from the other two domains also appear to contribute to the binding pocket. Residues that appear to interact with the substrate by hydrogen bonding include Gly48, Thr93, Trp135, Asn181, Glu182, Glu258, Ser261, and Arg380. Of particular interest are the residues Glu258 and Glu182, which have been proposed as the active site nucleophile and proton donor respectively, due to the average distance between the carboxyl oxygens being consistent with the retaining mechanism of glycosidic bond hydrolysis.<ref name=Deane>PMID: 21876145</ref>

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Because Krabbe disease is caused by a ''decrease'' in galactosylceramidase activity, there are no drug-protein interactions to explore. However some natural inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="()"}
- Twelve.
+ Forty-One.
- Sixty.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-05T01:23:57Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref name=PDB>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa monomer consisting of a 656 residues, which form a <scene name='58/587874/Galactosylceramidase_secondary/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref name=PDB>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>. The TIM barrel is composed of eight parallel β-strands surrounded by α-helices and a single disulfide bridge between residues Cys 271 and Cys 378, while the β-sandwich is composed of two twisted β-sheets. The lectin domain is characterized by a calcium ion that is bound in pentagonal bipyramidal configuration<ref name=Deane>PMID: 21876145</ref>.

The substrate-binding site of GALC is mostly comprised of the central TIM barrel, however loops from the other two domains also appear to contribute to the binding pocket. Residues that appear to interact with the substrate by hydrogen bonding include Gly48, Thr93, Trp135, Asn181, Glu182, Glu258, Ser261, and Arg380. Of particular interest are the residues Glu258 and Glu182, which have been proposed as the active site nucleophile and proton donor respectively, due to the average distance between the carboxyl oxygens being consistent with the retaining mechanism of glycosidic bond hydrolysis.<ref name=Deane>PMID: 21876145</ref>

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Because Krabbe disease is caused by a ''decrease'' in galactosylceramidase activity, there are no drug-protein interactions to explore. However some natural inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="()"}
- Twelve.
+ Forty-One.
- Sixty.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-04T18:34:28Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref name=PDB>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa monomer consisting of a 656 residues, which form a <scene name='58/587874/Galactosylceramidase_secondary/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref name=PDB>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="()"}
- Twelve.
+ Forty-One.
- Sixty.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-04T18:19:09Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa monomer consisting of a 656 residues, which form a <scene name='58/587874/Galactosylceramidase_secondary/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="()"}
- Twelve.
+ Forty-One.
- Sixty.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-04T18:17:10Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.


{{STRUCTURE_3zr5| PDB=3zr5 | SCENE= |CAPTION=Galactosylceramidase, [[3zr5]] }}

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa monomer consisting of a 656 residues, which form a <scene name='58/587874/Galactosylceramidase_secondary/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="()"}
- Twelve.
+ Forty-One.
- Sixty.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-04T18:13:50Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa monomer consisting of a 656 residues, which form a <scene name='58/587874/Galactosylceramidase_secondary/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="()"}
- Twelve.
+ Forty-One.
- Sixty.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-04T18:03:35Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a <scene name='58/587874/Galactosylceramidase_secondary/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="()"}
- Twelve.
+ Forty-One.
- Sixty.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:56:50Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a <scene name='58/587874/Galactosylceramidase_secondary/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="[]"}
- Twelve.
+ Forty-One.
- Sixty.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:55:36Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

{{STRUCTURE_3zr5 | PDB=3zr5}}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a <scene name='58/587874/Galactosylceramidase_secondary/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="[]"}
- Twelve.
+ Forty-One.
- Sixty.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:55:09Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

{{STRUCTURE_3ZR5 | PDB=3ZR5}}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a <scene name='58/587874/Galactosylceramidase_secondary/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="[]"}
- Twelve.
+ Forty-One.
- Sixty.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:53:00Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a <scene name='58/587874/Galactosylceramidase_secondary/1'>secondary structure</scene> containing 12 α-helices and 41 β-strands<ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref>. Each β-strand contains three to eleven residues. The enzyme contains three major domains: a central triosephosphate isomerase (TIM) barrel, a β-sandwich domain, and a lectin domain<ref name=Deane>PMID: 21876145</ref>.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many ß-strands are in this structure?
|type="[]"}
- Twelve.
+ Forty-One.
- Sixty.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:52:05Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

==Quiz==
<quiz display=simple>
{How many alpha helices are in this structure?
|type="[]"}
- Twelve.
+ Forty-One.
- Sixty.
</quiz>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:45:20Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

{|class="wikitable"
| Name = Galactosylceramidase
| image =
| image_source =
| PDB =
| HGNCid = 4115
| MGIid = 95636
| Symbol = GALC
| AltSymbols =
| IUPHAR =
| ChEMBL =
| OMIM = 606890
| ECnumber = 3.2.1.46
| Homologene = 124
| GeneAtlas_image1 =
| GeneAtlas_image2 =
| GeneAtlas_image3 =
| Protein_domain_image =
| Function = {{GNF_GO|id=GO:0004336 |text = galactosylceramidase activity}}
| Component = {{GNF_GO|id=GO:0005764 |text = lysosome}} {{GNF_GO|id=GO:0043202 |text = lysosomal lumen}}
| Process = {{GNF_GO|id=GO:0005975 |text = carbohydrate metabolic process}} {{GNF_GO|id=GO:0006665 |text = sphingolipid metabolic process}} {{GNF_GO|id=GO:0006683 |text = galactosylceramide catabolic process}} {{GNF_GO|id=GO:0006687 |text = glycosphingolipid metabolic process}} {{GNF_GO|id=GO:0044281 |text = small molecule metabolic process}}
| Hs_EntrezGene = 2581
| Hs_Ensembl = ENSG00000054983
| Hs_RefseqmRNA = NM_000153
| Hs_RefseqProtein = NP_000144
| Hs_GenLoc_db = hg19
| Hs_GenLoc_chr = 14
| Hs_GenLoc_start = 88304164
| Hs_GenLoc_end = 88460009
| Hs_Uniprot = P54803
| Mm_EntrezGene = 14420
| Mm_Ensembl = ENSMUSG00000021003
| Mm_RefseqmRNA = NM_008079
| Mm_RefseqProtein = NP_032105
| Mm_GenLoc_db = mm9
| Mm_GenLoc_chr = 12
| Mm_GenLoc_start = 98202304
| Mm_GenLoc_end = 98259459
| Mm_Uniprot = P54818
| path = PBB/2581
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:44:55Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

{{class="wikitable"
| Name = Galactosylceramidase
| image =
| image_source =
| PDB =
| HGNCid = 4115
| MGIid = 95636
| Symbol = GALC
| AltSymbols =
| IUPHAR =
| ChEMBL =
| OMIM = 606890
| ECnumber = 3.2.1.46
| Homologene = 124
| GeneAtlas_image1 =
| GeneAtlas_image2 =
| GeneAtlas_image3 =
| Protein_domain_image =
| Function = {{GNF_GO|id=GO:0004336 |text = galactosylceramidase activity}}
| Component = {{GNF_GO|id=GO:0005764 |text = lysosome}} {{GNF_GO|id=GO:0043202 |text = lysosomal lumen}}
| Process = {{GNF_GO|id=GO:0005975 |text = carbohydrate metabolic process}} {{GNF_GO|id=GO:0006665 |text = sphingolipid metabolic process}} {{GNF_GO|id=GO:0006683 |text = galactosylceramide catabolic process}} {{GNF_GO|id=GO:0006687 |text = glycosphingolipid metabolic process}} {{GNF_GO|id=GO:0044281 |text = small molecule metabolic process}}
| Hs_EntrezGene = 2581
| Hs_Ensembl = ENSG00000054983
| Hs_RefseqmRNA = NM_000153
| Hs_RefseqProtein = NP_000144
| Hs_GenLoc_db = hg19
| Hs_GenLoc_chr = 14
| Hs_GenLoc_start = 88304164
| Hs_GenLoc_end = 88460009
| Hs_Uniprot = P54803
| Mm_EntrezGene = 14420
| Mm_Ensembl = ENSMUSG00000021003
| Mm_RefseqmRNA = NM_008079
| Mm_RefseqProtein = NP_032105
| Mm_GenLoc_db = mm9
| Mm_GenLoc_chr = 12
| Mm_GenLoc_start = 98202304
| Mm_GenLoc_end = 98259459
| Mm_Uniprot = P54818
| path = PBB/2581
}}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:44:15Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

{{Protein_box
| Name = Galactosylceramidase
| image =
| image_source =
| PDB =
| HGNCid = 4115
| MGIid = 95636
| Symbol = GALC
| AltSymbols =
| IUPHAR =
| ChEMBL =
| OMIM = 606890
| ECnumber = 3.2.1.46
| Homologene = 124
| GeneAtlas_image1 =
| GeneAtlas_image2 =
| GeneAtlas_image3 =
| Protein_domain_image =
| Function = {{GNF_GO|id=GO:0004336 |text = galactosylceramidase activity}}
| Component = {{GNF_GO|id=GO:0005764 |text = lysosome}} {{GNF_GO|id=GO:0043202 |text = lysosomal lumen}}
| Process = {{GNF_GO|id=GO:0005975 |text = carbohydrate metabolic process}} {{GNF_GO|id=GO:0006665 |text = sphingolipid metabolic process}} {{GNF_GO|id=GO:0006683 |text = galactosylceramide catabolic process}} {{GNF_GO|id=GO:0006687 |text = glycosphingolipid metabolic process}} {{GNF_GO|id=GO:0044281 |text = small molecule metabolic process}}
| Hs_EntrezGene = 2581
| Hs_Ensembl = ENSG00000054983
| Hs_RefseqmRNA = NM_000153
| Hs_RefseqProtein = NP_000144
| Hs_GenLoc_db = hg19
| Hs_GenLoc_chr = 14
| Hs_GenLoc_start = 88304164
| Hs_GenLoc_end = 88460009
| Hs_Uniprot = P54803
| Mm_EntrezGene = 14420
| Mm_Ensembl = ENSMUSG00000021003
| Mm_RefseqmRNA = NM_008079
| Mm_RefseqProtein = NP_032105
| Mm_GenLoc_db = mm9
| Mm_GenLoc_chr = 12
| Mm_GenLoc_start = 98202304
| Mm_GenLoc_end = 98259459
| Mm_Uniprot = P54818
| path = PBB/2581
}}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:43:20Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

{{GNF_Protein_box
| Name = Galactosylceramidase
| image =
| image_source =
| PDB =
| HGNCid = 4115
| MGIid = 95636
| Symbol = GALC
| AltSymbols =
| IUPHAR =
| ChEMBL =
| OMIM = 606890
| ECnumber = 3.2.1.46
| Homologene = 124
| GeneAtlas_image1 =
| GeneAtlas_image2 =
| GeneAtlas_image3 =
| Protein_domain_image =
| Function = {{GNF_GO|id=GO:0004336 |text = galactosylceramidase activity}}
| Component = {{GNF_GO|id=GO:0005764 |text = lysosome}} {{GNF_GO|id=GO:0043202 |text = lysosomal lumen}}
| Process = {{GNF_GO|id=GO:0005975 |text = carbohydrate metabolic process}} {{GNF_GO|id=GO:0006665 |text = sphingolipid metabolic process}} {{GNF_GO|id=GO:0006683 |text = galactosylceramide catabolic process}} {{GNF_GO|id=GO:0006687 |text = glycosphingolipid metabolic process}} {{GNF_GO|id=GO:0044281 |text = small molecule metabolic process}}
| Hs_EntrezGene = 2581
| Hs_Ensembl = ENSG00000054983
| Hs_RefseqmRNA = NM_000153
| Hs_RefseqProtein = NP_000144
| Hs_GenLoc_db = hg19
| Hs_GenLoc_chr = 14
| Hs_GenLoc_start = 88304164
| Hs_GenLoc_end = 88460009
| Hs_Uniprot = P54803
| Mm_EntrezGene = 14420
| Mm_Ensembl = ENSMUSG00000021003
| Mm_RefseqmRNA = NM_008079
| Mm_RefseqProtein = NP_032105
| Mm_GenLoc_db = mm9
| Mm_GenLoc_chr = 12
| Mm_GenLoc_start = 98202304
| Mm_GenLoc_end = 98259459
| Mm_Uniprot = P54818
| path = PBB/2581
}}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:42:39Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

{{Template:PBB/2581}}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:40:30Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene ''GALC'', and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:38:07Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
'''Galactosylceramidase''' (or '''galactocerebrosidase''') (GALC) is a hydrolase enzyme<ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

{{enzyme
| Name = Galactosylceramidase
| EC_number = 3.2.1.46
| CAS_number = 9027-89-8
| IUBMB_EC_number = 3/2/1/46
| GO_code = 0004336
| image =
| width =
| caption =
}}
{{PBB|geneid=2581}}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:25:30Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

GALC

2014-06-04T17:25:00Z

Alison Stivers: Redirecting to Galactosylceramidase

#REDIRECT [[Galactosylceramidase]]

Galactocerebrosidase

2014-06-04T17:23:59Z

Alison Stivers: Redirecting to Galactosylceramidase

#REDIRECT [[Galactosylceramidase]]

Galactosylceramidase

2014-06-04T17:19:03Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref>, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:18:31Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane> PMID: 21876145 </ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri> PMID: 23983033 </ref><ref name=Kohlschutter>PMID: 23622382</ref<, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira> PMID: 24607884 </ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira> PMID: 24607884 </ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter> PMID: 23622382 </ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri> PMID: 23983033 </ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter> PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T17:17:01Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref<, by causing lipid raft clustering which leads to defective signal transduction<ref name=Teixeira>PMID: 24607884</ref>. Besides the defective recruitment of signal molecules to lipid rafts, there is also impairment in the early steps of endocytosis and vesicle transport<ref name=Teixeira>PMID: 24607884</ref>. Defects in the retrograde axonal transport is correlated with decreased amounts of dynein, unusual levels of post-translational tubulin modifications, and microtubule instability<ref name=Teixeira>PMID: 24607884</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T04:49:22Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|thumb|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T04:48:32Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|center|300px|NAG-galactosylceramidase ligand-enzyme interaction]]
==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T04:46:27Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine
[[Image:NAG-galactosylceramidase.jpg|center|550px|NAG-galactosylceramidase ligand-enzyme interaction]]
==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

File:NAG-galactosylceramidase.jpg

2014-06-04T04:44:59Z

Alison Stivers: NAG-galactosylceramidase ligand-enzyme interaction

== Summary ==
NAG-galactosylceramidase ligand-enzyme interaction
== Licensing ==
{{PD-self}}

Galactosylceramidase

2014-06-04T04:30:33Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px|Reaction of galactosylceramide and water catalyzed by galactosylceramidase]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T04:29:08Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|800px]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T04:27:54Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|600px]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T04:27:11Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb|center|500px]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T04:26:03Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg|thumb]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T04:24:54Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-04T04:22:46Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
[[Image:Reaction of galactosylceramide and water.jpg thumb|center|alt=Reaction of galactosylceramide and water catalyzed by galactosylceramidase.|Reaction of galactosylceramide and water catalyzed by galactosylceramidase.]]

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

File:Reaction of galactosylceramide and water.jpg

2014-06-04T04:18:40Z

Alison Stivers: Reaction of galactosylceramide and water catalyzed by galactosylceramidase

== Summary ==
Reaction of galactosylceramide and water catalyzed by galactosylceramidase
== Licensing ==
{{PD-self}}

Galactosylceramidase

2014-06-04T01:38:54Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Ligands==
*calcium ion
*N-acetyl-D-glucosamine

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-03T20:37:31Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
{{ABSTRACT_PUBMED_21876145}}

==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-03T20:33:30Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

== Function ==
The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. The cellular function is the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.

== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>

== References ==
<references/>

Galactosylceramidase

2014-06-03T20:26:41Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.
== Function ==
Galactosylceramidase hydrolyzes a O-glycosyl bond. It is involved in the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from www.brenda-enzymes.org</ref>
== References ==
<references/>

Galactosylceramidase

2014-06-03T20:25:56Z

Alison Stivers:

<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''>
Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>.

{| class="wikitable"
|-
| EC number
| 3.2.1.46
|-
| CAS number
| 158021-47-7
|-
| BRENDA
| [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46 BRENDA]
|-
| PDB
| [http://www.rcsb.org/pdb/explore.do?structureId=3zr5 3ZR5]
|-
| theoretical extinction coefficient
| 195,860 1/(M cm)
|-
| theoretical molecular weight
| 77.3 kDa
|-
| theoretical pI
| 6.27
|-
|}

==Structure==
X-ray diffraction data (<scene name='58/587874/Galactosylceramidase/1'>default scene</scene>) from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to <scene name="/12/3456/Sample/1">color</scene> by group, and this link to view a <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.
== Function ==
Galactosylceramidase hydrolyzes a O-glycosyl bond. It is involved in the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids<ref name=Visigalli> PMID: 20511539 </ref>.
== Disease ==
Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>.

== Relevance ==

</StructureSection>
==Inhibitors==
Inhibitory molecules in humans include:
*6-hexadecanoylamino-4-methylbelliferyl-beta-D-galactopyranoside, competitive inhibition
*D-galactose
*galactonyl hydrazide
*lactose
*N-(6-aminohexyl)-D-galactoside
*taurocholate (at high concentrations above 0.3% w/v)<ref name=BRENDA>EC 3.2.1.46 - galactosylceramidase. (n.d.). Information on. Retrieved June 3, 2014, from http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.2.1.46</ref>
== References ==
<references/>

Galactosylceramidase

2014-06-03T20:02:12Z

Alison Stivers:

Galactosylceramidase

2014-06-03T19:23:06Z

Alison Stivers:

Galactosylceramidase

2014-06-03T19:22:10Z

Alison Stivers:

Galactosylceramidase

2014-06-03T19:20:49Z

Alison Stivers:

Galactosylceramidase

2014-06-03T19:18:34Z

Alison Stivers:

Galactosylceramidase

2014-06-03T18:57:34Z

Alison Stivers: