2NSX

Structure of acid-beta-glucosidase with pharmacological chaperone provides insight into Gaucher disease

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d2nsxa1	All beta proteins	Glycosyl hydrolase domain	Glycosyl hydrolase domain	Composite domain of glycosyl hydrolase families 5, 30, 39 and 51	Glucosylceramidase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d2nsxa2	Alpha and beta proteins (a/b)	TIM beta/alpha-barrel	(Trans)glycosidases	beta-glycanases	Glucosylceramidase, catalytic domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2nsxb1	All beta proteins	Glycosyl hydrolase domain	Glycosyl hydrolase domain	Composite domain of glycosyl hydrolase families 5, 30, 39 and 51	Glucosylceramidase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2nsxb2	Alpha and beta proteins (a/b)	TIM beta/alpha-barrel	(Trans)glycosidases	beta-glycanases	Glucosylceramidase, catalytic domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d2nsxc1	All beta proteins	Glycosyl hydrolase domain	Glycosyl hydrolase domain	Composite domain of glycosyl hydrolase families 5, 30, 39 and 51	Glucosylceramidase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d2nsxc2	Alpha and beta proteins (a/b)	TIM beta/alpha-barrel	(Trans)glycosidases	beta-glycanases	Glucosylceramidase, catalytic domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d2nsxd1	All beta proteins	Glycosyl hydrolase domain	Glycosyl hydrolase domain	Composite domain of glycosyl hydrolase families 5, 30, 39 and 51	Glucosylceramidase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d2nsxd2	Alpha and beta proteins (a/b)	TIM beta/alpha-barrel	(Trans)glycosidases	beta-glycanases	Glucosylceramidase, catalytic domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	(Trans)glycosidases	8043254	3000313	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Glycosyl hydrolase domain-like	8043253	3001528	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Glycosyl hydrolase domain-like	8043253	3001528	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	(Trans)glycosidases	8043254	3000313	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Glycosyl hydrolase domain-like	8043253	3001528	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Glycosyl hydrolase domain-like	8043253	3001528	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Glycosyl hydrolase domain-like	8043253	3001528	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	(Trans)glycosidases	8043254	3000313	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Glycosyl hydrolase domain-like	8043253	3001528	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Glycosyl hydrolase domain-like	8043253	3001528	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Glycosyl hydrolase domain-like	8043253	3001528	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	(Trans)glycosidases	8043254	3000313	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Glyco_hydro_30C	e2nsxA1	A: beta sandwiches	X: Glycosyl hydrolase domain-like	H: Glycosyl hydrolase domain (From Topology)	T: Glycosyl hydrolase domain	F: Glyco_hydro_30C	ECOD (1.6)
A	Glyco_hydro_30	e2nsxA2	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: Glyco_hydro_30	ECOD (1.6)
B	Glyco_hydro_30C	e2nsxB1	A: beta sandwiches	X: Glycosyl hydrolase domain-like	H: Glycosyl hydrolase domain (From Topology)	T: Glycosyl hydrolase domain	F: Glyco_hydro_30C	ECOD (1.6)
B	Glyco_hydro_30	e2nsxB2	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: Glyco_hydro_30	ECOD (1.6)
C	Glyco_hydro_30C	e2nsxC1	A: beta sandwiches	X: Glycosyl hydrolase domain-like	H: Glycosyl hydrolase domain (From Topology)	T: Glycosyl hydrolase domain	F: Glyco_hydro_30C	ECOD (1.6)
C	Glyco_hydro_30	e2nsxC2	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: Glyco_hydro_30	ECOD (1.6)
D	Glyco_hydro_30C	e2nsxD1	A: beta sandwiches	X: Glycosyl hydrolase domain-like	H: Glycosyl hydrolase domain (From Topology)	T: Glycosyl hydrolase domain	F: Glyco_hydro_30C	ECOD (1.6)
D	Glyco_hydro_30	e2nsxD2	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: Glyco_hydro_30	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.20.20.80	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Glycosidases	CATH (4.3.0)
A	2.60.40.1180	Mainly Beta	Sandwich	Immunoglobulin-like	Golgi alpha-mannosidase II	CATH (4.3.0)
B	3.20.20.80	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Glycosidases	CATH (4.3.0)
B	2.60.40.1180	Mainly Beta	Sandwich	Immunoglobulin-like	Golgi alpha-mannosidase II	CATH (4.3.0)
C	3.20.20.80	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Glycosidases	CATH (4.3.0)
C	2.60.40.1180	Mainly Beta	Sandwich	Immunoglobulin-like	Golgi alpha-mannosidase II	CATH (4.3.0)
D	3.20.20.80	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Glycosidases	CATH (4.3.0)
D	2.60.40.1180	Mainly Beta	Sandwich	Immunoglobulin-like	Golgi alpha-mannosidase II	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF17189	Glycosyl hydrolase family 30 beta sandwich domain (Glyco_hydro_30C)	Glycosyl hydrolase family 30 beta sandwich domain	-	Domain
A, B, C, D	PF02055	Glycosyl hydrolase family 30 TIM-barrel domain (Glyco_hydro_30)	Glycosyl hydrolase family 30 TIM-barrel domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	Glucosylceramidase	glycosyltransferase activity transferase activity glucosyltransferase activity hexosyltransferase activity catalytic activity glucosylceramidase activity hydrolase activity, acting on glycosyl bonds hydrolase activity, hydrolyzing O-glycosyl compounds hydrolase activity protein binding binding signaling receptor binding scavenger receptor binding glucosidase activity glycosyltransferase activity transferase activity glucosyltransferase activity hexosyltransferase activity catalytic activity glucosylceramidase activity hydrolase activity, acting on glycosyl bonds hydrolase activity, hydrolyzing O-glycosyl compounds hydrolase activity protein binding binding signaling receptor binding scavenger receptor binding glucosidase activity steryl-beta-glucosidase activity beta-glucosidase activity galactosylceramidase activity	developmental process stem cell proliferation cell population proliferation cellular developmental process hemopoiesis cell differentiation anatomical structure development hematopoietic stem cell proliferation cell development cellular process cellular component disassembly regulation of biological process positive regulation of cellular component organization regulation of cellular process developmental process stem cell proliferation cell population proliferation cellular developmental process hemopoiesis cell differentiation anatomical structure development hematopoietic stem cell proliferation cell development cellular process cellular component disassembly regulation of biological process positive regulation of cellular component organization regulation of cellular process regulation of cellular component organization protein-containing complex organization biological regulation positive regulation of biological process protein-containing complex disassembly regulation of protein-containing complex disassembly cellular component organization cellular component organization or biogenesis positive regulation of protein-containing complex disassembly positive regulation of cellular process catabolic process macroautophagy cellular metabolic process autophagy regulation of cellular metabolic process regulation of catabolic process regulation of autophagy cellular catabolic process regulation of macroautophagy regulation of cellular catabolic process metabolic process regulation of metabolic process process utilizing autophagic mechanism interleukin-6 production multicellular organismal process cellular biosynthetic process negative regulation of biological process negative regulation of cellular metabolic process regulation of interleukin-6 production organic substance metabolic process regulation of cytokine production organic substance biosynthetic process cytokine production negative regulation of cellular process regulation of multicellular organismal process negative regulation of macromolecule metabolic process regulation of biosynthetic process negative regulation of metabolic process negative regulation of cytokine production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process negative regulation of cellular biosynthetic process regulation of cellular biosynthetic process regulation of gene expression negative regulation of interleukin-6 production negative regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process macromolecule metabolic process negative regulation of multicellular organismal process cellular response to stimulus response to stimulus regulation of catalytic activity negative regulation of catalytic activity regulation of signal transduction regulation of transferase activity regulation of MAP kinase activity intracellular signal transduction regulation of primary metabolic process cell communication negative regulation of kinase activity negative regulation of transferase activity regulation of phosphate metabolic process phosphate-containing compound metabolic process intracellular signaling cassette negative regulation of protein modification process signal transduction phosphorus metabolic process protein modification process negative regulation of protein metabolic process protein phosphorylation phosphorylation regulation of protein metabolic process primary metabolic process regulation of MAPK cascade regulation of molecular function regulation of kinase activity regulation of response to stimulus negative regulation of protein phosphorylation regulation of protein serine/threonine kinase activity macromolecule modification regulation of phosphorus metabolic process regulation of protein modification process regulation of protein phosphorylation signaling negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of phosphate metabolic process negative regulation of cell communication regulation of intracellular signal transduction negative regulation of protein serine/threonine kinase activity protein metabolic process regulation of signaling organonitrogen compound metabolic process negative regulation of response to stimulus negative regulation of molecular function negative regulation of MAP kinase activity regulation of protein kinase activity negative regulation of protein kinase activity negative regulation of signal transduction negative regulation of phosphorus metabolic process MAPK cascade regulation of cell communication regulation of phosphorylation negative regulation of phosphorylation negative regulation of MAPK cascade cerebellar cortex morphogenesis hindbrain morphogenesis cerebellar Purkinje cell layer formation multicellular organism development cerebellar Purkinje cell layer development metencephalon development cerebellar Purkinje cell layer morphogenesis cerebellar cortex formation system development cerebellum morphogenesis head development animal organ development brain development nervous system development cerebellar cortex development anatomical structure morphogenesis cerebellum development central nervous system development anatomical structure formation involved in morphogenesis hindbrain development establishment of skin barrier epithelium development skin development skin epidermis development epidermis development tissue development response to organic substance response to ketone response to lipid response to chemical response to oxygen-containing compound response to testosterone response to organic cyclic compound positive regulation of proteasomal protein catabolic process positive regulation of protein metabolic process proteolysis involved in protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process regulation of ubiquitin-dependent protein catabolic process positive regulation of metabolic process positive regulation of ubiquitin-dependent protein catabolic process regulation of proteolysis regulation of proteolysis involved in protein catabolic process modification-dependent macromolecule catabolic process proteolysis positive regulation of macromolecule metabolic process organonitrogen compound catabolic process proteasomal protein catabolic process protein catabolic process positive regulation of protein catabolic process positive regulation of proteolysis involved in protein catabolic process positive regulation of catabolic process regulation of proteasomal ubiquitin-dependent protein catabolic process modification-dependent protein catabolic process positive regulation of proteolysis regulation of proteasomal protein catabolic process positive regulation of proteasomal ubiquitin-dependent protein catabolic process ubiquitin-dependent protein catabolic process organic substance catabolic process regulation of protein catabolic process negative regulation of cellular component organization regulation of cellular component biogenesis negative regulation of protein-containing complex assembly cellular component biogenesis regulation of protein-containing complex assembly cellular component assembly protein-containing complex assembly system process nervous system process neuromuscular process cell activation mononuclear cell differentiation lymphocyte activation lymphocyte differentiation leukocyte activation T cell differentiation in thymus T cell activation immune system process T cell differentiation leukocyte differentiation cellular response to nutrient levels response to nutrient levels cellular response to stress response to stress response to starvation cellular response to starvation regulation of autophagy of mitochondrion in response to mitochondrial depolarization organelle organization organelle disassembly response to mitochondrial depolarisation positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization autophagy of mitochondrion mitochondrion organization response to endogenous stimulus response to glucocorticoid response to corticosteroid response to hormone response to steroid hormone response to dexamethasone regulation of protein catabolic process in the vacuole lysosomal protein catabolic process protein catabolic process in the vacuole regulation of lysosomal protein catabolic process sphingolipid catabolic process glycolipid metabolic process carbohydrate derivative metabolic process cellular lipid catabolic process ceramide catabolic process amide metabolic process glycosylceramide metabolic process membrane lipid metabolic process ceramide metabolic process carbohydrate derivative catabolic process glycosphingolipid catabolic process lipid catabolic process glycosphingolipid metabolic process liposaccharide metabolic process sphingolipid metabolic process glucosylceramide metabolic process membrane lipid catabolic process glycosylceramide catabolic process glycolipid catabolic process cellular lipid metabolic process glucosylceramide catabolic process lipid metabolic process positive regulation of cell communication regulation of system process positive regulation of transmission of nerve impulse neuronal action potential regulation of transmission of nerve impulse positive regulation of nervous system process regulation of biological quality regulation of neuronal action potential regulation of action potential action potential transmission of nerve impulse regulation of nervous system process positive regulation of action potential positive regulation of multicellular organismal process positive regulation of neuronal action potential regulation of membrane potential response to estrogen multicellular organismal-level homeostasis homeostatic process homeostasis of number of cells sphingolipid biosynthetic process organic hydroxy compound metabolic process organonitrogen compound biosynthetic process lipid biosynthetic process alcohol metabolic process diol biosynthetic process diol metabolic process polyol biosynthetic process small molecule metabolic process sphingoid biosynthetic process polyol metabolic process small molecule biosynthetic process sphingosine metabolic process sphingoid metabolic process sphingosine biosynthetic process organic hydroxy compound biosynthetic process alcohol biosynthetic process membrane lipid biosynthetic process glycosyl compound metabolic process glycoside metabolic process glycosyl compound catabolic process glycoside catabolic process beta-glucoside catabolic process beta-glucoside metabolic process amide biosynthetic process ceramide biosynthetic process brain morphogenesis animal organ morphogenesis leukocyte migration mononuclear cell migration lymphocyte migration cell migration cell motility regulation of defense response regulation of response to external stimulus negative regulation of inflammatory response defense response response to external stimulus regulation of inflammatory response negative regulation of response to external stimulus regulation of response to stress negative regulation of defense response inflammatory response termination of signal transduction sterol metabolic process steroid metabolic process cholesterol metabolic process organic cyclic compound metabolic process secondary alcohol metabolic process neuron apoptotic process negative regulation of neuron apoptotic process negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death regulation of neuron apoptotic process lysosome organization vacuole organization lytic vacuole organization myeloid leukocyte differentiation macrophage differentiation neurogenesis gliogenesis glial cell differentiation myeloid cell differentiation microglia differentiation anatomical structure maturation cell maturation developmental maturation response to cytokine cellular response to chemical stimulus cellular response to tumor necrosis factor cellular response to cytokine stimulus cellular response to organic substance response to tumor necrosis factor response to pH response to abiotic stimulus determination of adult lifespan response to thyroid hormone glycosylation lipid glycosylation lipid modification localization macromolecule localization lipid storage lipid localization maintenance of location generation of neurons neuron differentiation pyramidal neuron differentiation microglial cell proliferation leukocyte proliferation macrophage proliferation glial cell proliferation behavior motor behavior protein dephosphorylation positive regulation of cellular metabolic process positive regulation of phosphate metabolic process positive regulation of protein modification process positive regulation of phosphorus metabolic process positive regulation of dephosphorylation regulation of dephosphorylation regulation of protein dephosphorylation dephosphorylation positive regulation of protein dephosphorylation antigen processing and presentation TOR signaling regulation of TOR signaling cellular respiration energy derivation by oxidation of organic compounds respiratory electron transport chain electron transport chain generation of precursor metabolites and energy lipoprotein biosynthetic process lipoprotein metabolic process protein lipidation positive regulation of lipoprotein metabolic process positive regulation of biosynthetic process positive regulation of protein lipidation regulation of lipoprotein metabolic process regulation of protein lipidation positive regulation of cellular biosynthetic process autophagosome organization	extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle vacuolar membrane intracellular anatomical structure membrane lytic vacuole extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle vacuolar membrane intracellular anatomical structure membrane lytic vacuole vacuole intracellular membrane-bounded organelle intracellular organelle lytic vacuole membrane bounding membrane of organelle lysosomal membrane cytoplasm organelle membrane lysosome Golgi apparatus subcompartment Golgi apparatus organelle subcompartment endomembrane system trans-Golgi network membrane-enclosed lumen vacuolar lumen lysosomal lumen intracellular organelle lumen organelle lumen endoplasmic reticulum

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR033452	Glycosyl hydrolase family 30, beta sandwich domain	Domain
A, B, C, D	IPR001139	Glycoside hydrolase family 30	Family
A, B, C, D	IPR017853	Glycoside hydrolase superfamily	Homologous Superfamily
A, B, C, D	IPR033453	Glycosyl hydrolase family 30, TIM-barrel domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: P04062	Gaucher disease Parkinson disease Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome Lewy body dementia Gaucher disease perinatal lethal late-onset Parkinson disease Gaucher disease type II pulmonary hypertension Gaucher disease type III Gaucher disease type I Gaucher Disease, Type 2 (disorder) arthrogryposis mucolipidosis type IV brain aneurysm Crohn disease Gaucher disease Parkinson disease Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome Lewy body dementia Gaucher disease perinatal lethal late-onset Parkinson disease Gaucher disease type II pulmonary hypertension Gaucher disease type III Gaucher disease type I Gaucher Disease, Type 2 (disorder) arthrogryposis mucolipidosis type IV brain aneurysm Crohn disease psoriasis Riley-Day syndrome hematopoietic and lymphoid system neoplasm inborn errors of metabolism autosomal recessive juvenile Parkinson disease 2 neurodegenerative disease cholestasis parkinsonian disorder dental caries hydrops fetalis intellectual disability lysosomal storage disease Niemann-Pick disease type B diabetes mellitus gastric adenocarcinoma sphingolipidosis

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.