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| - | {{STRUCTURE_4do5| PDB=4do5 | SCENE= }} | |
| - | ===Pharmacological chaperones for human alpha-N-acetylgalactosaminidase=== | |
| - | {{ABSTRACT_PUBMED_23045655}} | |
| | | | |
| - | ==Disease== | + | ==Pharmacological chaperones for human alpha-N-acetylgalactosaminidase== |
| - | [[http://www.uniprot.org/uniprot/NAGAB_HUMAN NAGAB_HUMAN]] Defects in NAGA are the cause of Schindler disease (SCHIND) [MIM:[http://omim.org/entry/609241 609241]]. Schindler disease is a form of NAGA deficiency characterized by early onset neuroaxonal dystrophy and neurological signs (convulsion during fever, epilepsy, psychomotor retardation and hypotonia). NAGA deficiency is typically classified in three main phenotypes: NAGA deficiency type I (Schindler disease or Schindler disease type I) with severe manifestations; NAGA deficiency type II (Kanzazi disease or Schindler disease type II) which is mild; NAGA deficiency type III (Schindler disease type III) characterized by mild-to-moderate neurologic manifestations. NAGA deficiency results in the increased urinary excretion of glycopeptides and oligosaccharides containing alpha-N-acetylgalactosaminyl moieties. Inheritance is autosomal recessive.<ref>PMID:2243144</ref><ref>PMID:8782044</ref> Defects in NAGA are the cause of Kanzaki disease (KANZD) [MIM:[http://omim.org/entry/609242 609242]]; also known as NAGA deficiency type II or Schindler disease type II. Kanzaki disease is an autosomal recessive disorder characterized by late onset, angiokeratoma corporis diffusum and mild intellectual impairment.<ref>PMID:8040340</ref><ref>PMID:11251574</ref> | + | <StructureSection load='4do5' size='340' side='right'caption='[[4do5]], [[Resolution|resolution]] 1.51Å' scene=''> |
| - | | + | == Structural highlights == |
| - | ==Function== | + | <table><tr><td colspan='2'>[[4do5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DO5 FirstGlance]. <br> |
| - | [[http://www.uniprot.org/uniprot/NAGAB_HUMAN NAGAB_HUMAN]] Removes terminal alpha-N-acetylgalactosamine residues from glycolipids and glycopeptides. Required for the breakdown of glycolipids.<ref>PMID:9741689</ref> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.51Å</td></tr> |
| - | | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=DGJ:(2R,3S,4R,5S)-2-(HYDROXYMETHYL)PIPERIDINE-3,4,5-TRIOL'>DGJ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | ==About this Structure== | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4do5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4do5 OCA], [https://pdbe.org/4do5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4do5 RCSB], [https://www.ebi.ac.uk/pdbsum/4do5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4do5 ProSAT]</span></td></tr> |
| - | [[4do5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DO5 OCA].
| + | </table> |
| - | | + | == Disease == |
| - | ==Reference==
| + | [https://www.uniprot.org/uniprot/NAGAB_HUMAN NAGAB_HUMAN] Defects in NAGA are the cause of Schindler disease (SCHIND) [MIM:[https://omim.org/entry/609241 609241]. Schindler disease is a form of NAGA deficiency characterized by early onset neuroaxonal dystrophy and neurological signs (convulsion during fever, epilepsy, psychomotor retardation and hypotonia). NAGA deficiency is typically classified in three main phenotypes: NAGA deficiency type I (Schindler disease or Schindler disease type I) with severe manifestations; NAGA deficiency type II (Kanzazi disease or Schindler disease type II) which is mild; NAGA deficiency type III (Schindler disease type III) characterized by mild-to-moderate neurologic manifestations. NAGA deficiency results in the increased urinary excretion of glycopeptides and oligosaccharides containing alpha-N-acetylgalactosaminyl moieties. Inheritance is autosomal recessive.<ref>PMID:2243144</ref> <ref>PMID:8782044</ref> Defects in NAGA are the cause of Kanzaki disease (KANZD) [MIM:[https://omim.org/entry/609242 609242]; also known as NAGA deficiency type II or Schindler disease type II. Kanzaki disease is an autosomal recessive disorder characterized by late onset, angiokeratoma corporis diffusum and mild intellectual impairment.<ref>PMID:8040340</ref> <ref>PMID:11251574</ref> |
| - | <references group="xtra"/><references/> | + | == Function == |
| - | [[Category: Alpha-N-acetylgalactosaminidase]]
| + | [https://www.uniprot.org/uniprot/NAGAB_HUMAN NAGAB_HUMAN] Removes terminal alpha-N-acetylgalactosamine residues from glycolipids and glycopeptides. Required for the breakdown of glycolipids.<ref>PMID:9741689</ref> |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Clark, N E.]] | + | [[Category: Large Structures]] |
| - | [[Category: Garman, S C.]] | + | [[Category: Clark NE]] |
| - | [[Category: Carbohydrate-binding protein]] | + | [[Category: Garman SC]] |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Glycosidase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Lysosome]]
| + | |
| - | [[Category: Pharmacological chaperone]]
| + | |
| Structural highlights
4do5 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.51Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
NAGAB_HUMAN Defects in NAGA are the cause of Schindler disease (SCHIND) [MIM:609241. Schindler disease is a form of NAGA deficiency characterized by early onset neuroaxonal dystrophy and neurological signs (convulsion during fever, epilepsy, psychomotor retardation and hypotonia). NAGA deficiency is typically classified in three main phenotypes: NAGA deficiency type I (Schindler disease or Schindler disease type I) with severe manifestations; NAGA deficiency type II (Kanzazi disease or Schindler disease type II) which is mild; NAGA deficiency type III (Schindler disease type III) characterized by mild-to-moderate neurologic manifestations. NAGA deficiency results in the increased urinary excretion of glycopeptides and oligosaccharides containing alpha-N-acetylgalactosaminyl moieties. Inheritance is autosomal recessive.[1] [2] Defects in NAGA are the cause of Kanzaki disease (KANZD) [MIM:609242; also known as NAGA deficiency type II or Schindler disease type II. Kanzaki disease is an autosomal recessive disorder characterized by late onset, angiokeratoma corporis diffusum and mild intellectual impairment.[3] [4]
Function
NAGAB_HUMAN Removes terminal alpha-N-acetylgalactosamine residues from glycolipids and glycopeptides. Required for the breakdown of glycolipids.[5]
References
- ↑ Wang AM, Schindler D, Desnick R. Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy. J Clin Invest. 1990 Nov;86(5):1752-6. PMID:2243144 doi:http://dx.doi.org/10.1172/JCI114901
- ↑ Keulemans JL, Reuser AJ, Kroos MA, Willemsen R, Hermans MM, van den Ouweland AM, de Jong JG, Wevers RA, Renier WO, Schindler D, Coll MJ, Chabas A, Sakuraba H, Suzuki Y, van Diggelen OP. Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: new mutations and the paradox between genotype and phenotype. J Med Genet. 1996 Jun;33(6):458-64. PMID:8782044
- ↑ Wang AM, Kanzaki T, Desnick RJ. The molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes angiokeratoma corporis diffusum with glycopeptiduria. J Clin Invest. 1994 Aug;94(2):839-45. PMID:8040340 doi:http://dx.doi.org/10.1172/JCI117404
- ↑ Kodama K, Kobayashi H, Abe R, Ohkawara A, Yoshii N, Yotsumoto S, Fukushige T, Nagatsuka Y, Hirabayashi Y, Kanzaki T. A new case of alpha-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Meniere's syndrome and without mental retardation. Br J Dermatol. 2001 Feb;144(2):363-8. PMID:11251574
- ↑ Asfaw B, Schindler D, Ledvinova J, Cerny B, Smid F, Conzelmann E. Degradation of blood group A glycolipid A-6-2 by normal and mutant human skin fibroblasts. J Lipid Res. 1998 Sep;39(9):1768-80. PMID:9741689
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