Galactosidase

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{{STRUCTURE_3e1f| PDB=3e1f | SIZE=400| SCENE=Galactosidase/Cv/1 |right|CAPTION=E. coli β-galactosidase tetramer complex with β-D-galactose, DMSO, Mg+2 and Na+ ions, [[3e1f]] }}
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<StructureSection load='3w5g' size='350' side='right' caption='Glycosylated beta-galactosidase complex with galactose (PDB entry [[3w5g]])' scene=''>
== Function ==
== Function ==
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'''α-Galactosidase''' (Agal) hydrolyzes the terminal α-galactosyl moiety from glycoproteins and glycolipids<ref>PMID:15003450</ref>. '''β-Galactosidase''' (Bgal) hydrolyzes β-galactosides into monosaccharides<ref>PMID:8008071</ref>.
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'''α-Galactosidase''' (Agal) hydrolyzes the terminal α-galactosyl moiety from glycoproteins and glycolipids<ref>PMID:15003450</ref>.
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Isopropyl-β-d-thiogalactopyranoside (IPTG) induces Bgal activity. Phenylethyl-β-d-thiogalactopyranoside (PETG) is an inhibitor. Galactose, lactose, o-nitrophenyl-β-d-galactoside (ONPG) are substrates. Galactopyranosyl is reaction intermediate. For details on β-galactosidase see [[Molecular Playground/Beta-galactosidase]].
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*'''β-Galactosidase''' (Bgal) hydrolyzes β-galactosides into monosaccharides<ref>PMID:8008071</ref>.
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Isopropyl-β-d-thiogalactopyranoside (IPTG) induces Bgal activity. Phenylethyl-β-d-thiogalactopyranoside (PETG) is an inhibitor. Galactose, lactose, o-nitrophenyl-β-d-galactoside (ONPG) are substrates. Galactopyranosyl is reaction intermediate.<br /> For details on α-galactosidase see [[Garman lab: Interconversion of lysosomal enzyme specificities]].<br />For details on β-galactosidase see [[Molecular Playground/Beta-galactosidase]].
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See also: [[Beta-galactosidase (hebrew)]]
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*'''Endo-1,4-β-galactosidase''' hydrolyzes pectic galactans to produce D-galactose, beta-1,4-D galactobiose, beta-1,4-D galactotriose and beta-1,4-D galactotetraose<ref>PMID:16495677</ref>.
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== Disease ==
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See also [[Lactase (a protein)]]
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The inherited deficiency of Agal is the cause of Fabry disease<ref>PMID:5411915</ref>. Bgal deficiency can lead to galactosialidosis<ref>PMID:1683129</ref>.
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== Relevance ==
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== 3D Structures of Galactosidase ==
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Bgal assay is used in molecular biology to monitor gene expression.
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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== Disease ==
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*α-Galactosidase
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The inherited deficiency of Agal is the cause of Fabry disease<ref>PMID:5411915</ref>. Bgal mutations causing enzyme deficiency can lead to ganglioidosis<ref>PMID:10737981</ref>.
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**[[3lrk]] – yAgal 1 (mutant) – yeast<br />
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== Structural highlights ==
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**[[3lrl]], [[3lrm]] – yAgal 1 (mutant) + polysaccharide<br />
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**[[3lx9]], [[3lxa]], [[3lxb]], [[3lxc]], [[3tv8]] - hAgal A (mutant) – human<br />
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**[[3hg2]], [[3gxn]], [[1r46]], [[1r47]], [[3s5y]], [[3s5z]] – hAgal A<br />
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For [[3hg2]] <scene name='3hg2/3hg2to3morph/6'>click here to see cycling morph from empty active site to substrate bound form and back</scene>.<br />
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**[[1zy9]] – TmAgal – ''Thermotoga maritima''<br />
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**[[3h53]] - hAgal B (mutant)<br />
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**[[3a24]] – BtAgal – ''Bacterioides thetaiotamicron''<br />
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**[[3a5v]] – Agal I – ''Mortierella vinacea''<br />
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**[[3mi6]] – Agal – ''Lactobacillus brevis''<br />
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**[[1szn]] – HjAgal – ''Hypocrea jecorina''<br />
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**[[1uas]] – Agal – rice<br />
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**[[2xn0]], [[2xn1]] – LaAgal – ''Lactobacillus acidophilus''<br />
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**[[4fnp]], [[4ojy]] – GsAgal (mutant) – ''Geobacillus stearothermophilus''<br />
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**[[4fnq]], [[4fnr]], [[4oif]] – GsAgal
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*''α-galactosidase binary complex''
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The <scene name='45/458439/Cv/3'>Zn+2 binding site is composed of 4 Cys residues</scene>. The <scene name='45/458439/Cv/5'>galactose binding site</scene> is seen in a <scene name='45/458439/Cv/6'>large central channel</scene><ref>PMID:12215416</ref>. Water molecules shown as red spheres.
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**[[3h54]] - hAgal B (mutant) + polysaccharide<br />
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For [[3hg2]] <scene name='3hg2/3hg2to3morph/6'>click here to see cycling morph from empty active site to substrate bound form and back</scene>.<br />
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**[[3h55]] - hAgal B (mutant) + galactose<br />
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**[[3igu]] - hAgal B (mutant) + intermediate<br />
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**[[3hg3]], [[3hg5]] - hAgal A (mutant) + galactose<br />
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**[[3gxp]] - hAgal A + galactose<br />
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**[[3hg4]] – hAgal A + intermediate<br />
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**[[3gxt]] – hAgal A + imino sugar<br />
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**[[4nxs]] - hAgal + jirimycin derivative<br />
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**[[1t0o]] – HjAgal + galactose<br />
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**[[2xn2]] - LaAgal + galactose<br />
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**[[4fns]] - GsAgal (mutant) + jirimycin derivative<br />
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**[[4fnt]], [[4fnu]] – GsAgal + galactoside
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*β-Galactosidase
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== 3D Structures of Galactosidase ==
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[[Galactosidase 3D structures]]
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**[[3og2]] – TrBgal – ''Trichoderma reesei''<br />
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**[[3muy]], [[3i3e]], [[3iap]], [[3iaq]], [[3dyp]], [[1px3]], [[3sep]], [[3t0a]], [[3t2o]], [[3vd3]], [[3vd5]], [[3vda]], [[4duv]] – EcBgal (mutant) – ''Escherichia coli''<br />
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**[[1hn1]], [[1dp0]], [[1f49]], [[1f4a]], [[1f4h]], [[1gho]], [[1bgl]], [[1bgm]], [[4ttg]] - EcBgal<br />
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**[[3j7h]] – EcBgal – cryo EM<br />
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**[[3dec]], [[3d3a]], [[3bga]] – BtBgal<br />
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**[[1yq2]] - Bgal (mutant) – Arthrobacter<br />
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**[[1uwi]], [[4eam]] - SsBgal (mutant) - ''Sulfolobus solfataricus''<br />
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**[[1uwq]], [[4gow]] – SsBgal<br />
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**[[1kwg]] – TtBgal – ''Thermus thermophilus''<br />
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**[[1tg7]] – PeBgal – ''Penicillium''<br />
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**[[3tts]] – BcBgal – ''Bacillus circulans''<br />
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**[[4ha3]], [[4ha4]] – Bgal – ''Acidilobus saccharovorans''<br />
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**[[3w5f]] – toBgal – tomato<br />
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**[[3wq8]] – Bgal – ''Pyrococcus furiosus''<br />
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**[[4cu6]] – SpBgal catalytic module residues 137-985– ''Streptococcus pneumoniae''<br />
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**[[4cu9]] – SpBgal carbohydrate-binding module II residues 1822-1998 <br />
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**[[4cua]] – SpBgal carbohydrate-binding module I residues 1463-1645 <br />
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**[[4uoq]] - BaBgal (mutant) – ''Bifidobacterium animalis''<br />
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**[[3ob8]], [[3oba]] – Bgal – ''Kluyveromyces lactis''<br />
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*''β-Galactosidase binary complex with galactose''
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**[[1xc6]] - PeBgal + galactose<br />
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**[[3w5g]] - toBgal + galactose<br />
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**[[1kwk]] – TtBgal + galactose<br />
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**[[3ogr]] – TrBgal + galactose<br />
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**[[3e1f]], [[1jz7]] - EcBgal (mutant) + galactose<br />
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**[[3t09]], [[3t0d]], [[3t2q]], [[3vd7]], [[3vdb]] - EcBgal (mutant) + galactose derivative<br />
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**[[4iug]] - Bgal + galactose – ''Aspergillus oryzae''<br />
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**[[3tty]] - BcBgal + galactose<br />
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**[[3thc]] - hBgal + galactose<br />
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**[[3wf3]] - hBgal + galactose + NAG<br />
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**[[4cub]] – SpBgal carbohydrate-binding module I + galactose <br />
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**[[4cuc]] – SpBgal catalytic module (mutant) + galactose <br />
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**[[4uni]] - BaBgal + galactose <br />
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**[[4uoz]] - BaBgal (mutant) + galactose <br />
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*''β-Galactosidase other complexes''
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**[[3ogs]] - TrBgal + IPTG<br />
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**[[3ogv]] – TrBgal + inhibitor<br />
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**[[2ceq]], [[1uwr]], [[1uws]], [[1uwt]], [[1uwu]], [[2cer]] - SsBgal + inhibitor<br />
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**[[4ean]] – SsBgal + indole<br />
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**[[3muz]], [[3i3d]], [[3dyo]], [[1px4]], [[1jyx]], [[3t08]], [[3t0b]], [[3t2p]], [[3vd4]], [[3vd9]], [[3vdc]]- EcBgal (mutant) + IPTG<br />
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**[[3mv0]], [[3i3b]], [[3czj]], [[1jz0]], [[1jz1]], [[1jz2]], [[1jz3]], [[1jz4]], [[1jz5]], [[1jz6]] - EcBgal (mutant) + intermediate<br />
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**[[3mv1]] - EcBgal (mutant) + guanidinium<br />
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**[[1jyn]], [[1jyy]], [[1jyz]], [[1jz8]] - EcBgal (mutant) + lactose derivative<br />
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**[[1jyn]], [[1jyw]], [[1jyv]] - EcBgal (mutant) + substrate<br />
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**[[1jz6]] - EcBgal (mutant) + inhibitor<br />
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**[[4duw]] - EcBgal (mutant) + allolactose<br />
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**[[4dux]] - EcBgal (mutant) + ribose<br />
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**[[4ckd]] – EcBgal + antibody<br />
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**[[3thd]] – hBgal + jirimycin derivative<br />
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**[[3wez]] - hBgal + NOEV<br />
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**[[3wf0]], [[3wf1]] - hBgal + pyrimidine derivative<br />
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**[[3wf2]] - hBgal + piperidine derivative<br />
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**[[4cu7]] - SpBgal catalytic module + galacto-isofagomine<br />
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*Endo-1,4-β-galactosidase
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**[[2xom]], [[2xon]] – TmEbgal carbohydrate-binding domain + β-galactotriose<br />
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**[[1ups]] – Ebgal - ''Clostridium perfringens''<br />
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**[[2ygl]], [[2ygm]] – SpEbgal blood group A & B cleaving <br />
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**[[4bf7]] – Ebgal – ''Emericella nidulans''<br />
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*3,6-anhydro-α-L-galactosidase
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**[[3p2n]] – AAgal – ''Zobellia galactanivorans''<br />
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**[[4ak5]] – BpAAgal – ''Bacterioides plebeius''<br />
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**[[4ak6]] – BpAAgal (mutant)<br />
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**[[4ak7]] – BpAAgal (mutant) + polysaccharide<br />
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*6-phospho-β-D-galactosidase
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</StructureSection>
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**[[2pbg]], [[3pbg]], [[4pbg]], [[1pbg]] – Pgal (mutant) – ''Lactococcus lacti''<br />
 
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**[[2v4v]] – gal GH59 – ''Clostridium cellulolyticum''
 
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}}
 
== References ==
== References ==
<references/>
<references/>

Current revision

Glycosylated beta-galactosidase complex with galactose (PDB entry 3w5g)

Drag the structure with the mouse to rotate

References

  1. ↑ Garman SC, Garboczi DN. The molecular defect leading to Fabry disease: structure of human alpha-galactosidase. J Mol Biol. 2004 Mar 19;337(2):319-35. PMID:15003450 doi:10.1016/j.jmb.2004.01.035
  2. ↑ Jacobson RH, Zhang XJ, DuBose RF, Matthews BW. Three-dimensional structure of beta-galactosidase from E. coli. Nature. 1994 Jun 30;369(6483):761-6. PMID:8008071 doi:http://dx.doi.org/10.1038/369761a08015589
  3. ↑ Yang H, Ichinose H, Yoshida M, Nakajima M, Kobayashi H, Kaneko S. Characterization of a thermostable endo-beta-1,4-D-galactanase from the hyperthermophile Thermotoga maritima. Biosci Biotechnol Biochem. 2006 Feb;70(2):538-41. PMID:16495677 doi:10.1271/bbb.70.538
  4. ↑ Kint JA. Fabry's disease: alpha-galactosidase deficiency. Science. 1970 Feb 27;167(3922):1268-9. PMID:5411915
  5. ↑ Morrone A, Bardelli T, Donati MA, Giorgi M, Di Rocco M, Gatti R, Parini R, Ricci R, Taddeucci G, D'Azzo A, Zammarchi E. beta-galactosidase gene mutations affecting the lysosomal enzyme and the elastin-binding protein in GM1-gangliosidosis patients with cardiac involvement. Hum Mutat. 2000;15(4):354-66. PMID:10737981 doi:<354::AID-HUMU8>3.0.CO;2-L 10.1002/(SICI)1098-1004(200004)15:4<354::AID-HUMU8>3.0.CO;2-L
  6. ↑ Hidaka M, Fushinobu S, Ohtsu N, Motoshima H, Matsuzawa H, Shoun H, Wakagi T. Trimeric crystal structure of the glycoside hydrolase family 42 beta-galactosidase from Thermus thermophilus A4 and the structure of its complex with galactose. J Mol Biol. 2002 Sep 6;322(1):79-91. PMID:12215416


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