1o7a
From Proteopedia
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|PDB= 1o7a |SIZE=350|CAPTION= <scene name='initialview01'>1o7a</scene>, resolution 2.25Å | |PDB= 1o7a |SIZE=350|CAPTION= <scene name='initialview01'>1o7a</scene>, resolution 2.25Å | ||
|SITE= <scene name='pdbsite=ABC:N-Glycosylation+Site+3'>ABC</scene> | |SITE= <scene name='pdbsite=ABC:N-Glycosylation+Site+3'>ABC</scene> | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GDL:2-ACETAMIDO-2-DEOXY-D-GLUCONO-1,5-LACTONE'>GDL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Beta-N-acetylhexosaminidase Beta-N-acetylhexosaminidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.52 3.2.1.52] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-N-acetylhexosaminidase Beta-N-acetylhexosaminidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.52 3.2.1.52] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1o7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o7a OCA], [http://www.ebi.ac.uk/pdbsum/1o7a PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1o7a RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Human lysosomal beta-hexosaminidases are dimeric enzymes composed of alpha and beta-chains, encoded by the genes HEXA and HEXB. They occur in three isoforms, the homodimeric hexosaminidases B (betabeta) and S (alphaalpha), and the heterodimeric hexosaminidase A (alphabeta), where dimerization is required for catalytic activity. Allelic variations in the HEXA and HEXB genes cause the fatal inborn errors of metabolism Tay-Sachs disease and Sandhoff disease, respectively. Here, we present the crystal structure of a complex of human beta-hexosaminidase B with a transition state analogue inhibitor at 2.3A resolution (pdb 1o7a). On the basis of this structure and previous studies on related enzymes, a retaining double-displacement mechanism for glycosyl hydrolysis by beta-hexosaminidase B is proposed. In the dimer structure, which is derived from an analysis of crystal packing, most of the mutations causing late-onset Sandhoff disease reside near the dimer interface and are proposed to interfere with correct dimer formation. The structure reported here is a valid template also for the dimeric structures of beta-hexosaminidase A and S. | Human lysosomal beta-hexosaminidases are dimeric enzymes composed of alpha and beta-chains, encoded by the genes HEXA and HEXB. They occur in three isoforms, the homodimeric hexosaminidases B (betabeta) and S (alphaalpha), and the heterodimeric hexosaminidase A (alphabeta), where dimerization is required for catalytic activity. Allelic variations in the HEXA and HEXB genes cause the fatal inborn errors of metabolism Tay-Sachs disease and Sandhoff disease, respectively. Here, we present the crystal structure of a complex of human beta-hexosaminidase B with a transition state analogue inhibitor at 2.3A resolution (pdb 1o7a). On the basis of this structure and previous studies on related enzymes, a retaining double-displacement mechanism for glycosyl hydrolysis by beta-hexosaminidase B is proposed. In the dimer structure, which is derived from an analysis of crystal packing, most of the mutations causing late-onset Sandhoff disease reside near the dimer interface and are proposed to interfere with correct dimer formation. The structure reported here is a valid template also for the dimeric structures of beta-hexosaminidase A and S. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Sandhoff disease, infantile, juvenile, and adult forms OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606873 606873]], Spinal muscular atrophy, juvenile OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606873 606873]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Schuette, C.]] | [[Category: Schuette, C.]] | ||
[[Category: Strater, N.]] | [[Category: Strater, N.]] | ||
| - | [[Category: EDO]] | ||
| - | [[Category: GDL]] | ||
| - | [[Category: NAG]] | ||
[[Category: ba8-barrel]] | [[Category: ba8-barrel]] | ||
[[Category: glycosidase]] | [[Category: glycosidase]] | ||
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[[Category: sphingolipid degradation]] | [[Category: sphingolipid degradation]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:40:50 2008'' |
Revision as of 19:40, 30 March 2008
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| , resolution 2.25Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , | ||||||
| Activity: | Beta-N-acetylhexosaminidase, with EC number 3.2.1.52 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN BETA-HEXOSAMINIDASE B
Overview
Human lysosomal beta-hexosaminidases are dimeric enzymes composed of alpha and beta-chains, encoded by the genes HEXA and HEXB. They occur in three isoforms, the homodimeric hexosaminidases B (betabeta) and S (alphaalpha), and the heterodimeric hexosaminidase A (alphabeta), where dimerization is required for catalytic activity. Allelic variations in the HEXA and HEXB genes cause the fatal inborn errors of metabolism Tay-Sachs disease and Sandhoff disease, respectively. Here, we present the crystal structure of a complex of human beta-hexosaminidase B with a transition state analogue inhibitor at 2.3A resolution (pdb 1o7a). On the basis of this structure and previous studies on related enzymes, a retaining double-displacement mechanism for glycosyl hydrolysis by beta-hexosaminidase B is proposed. In the dimer structure, which is derived from an analysis of crystal packing, most of the mutations causing late-onset Sandhoff disease reside near the dimer interface and are proposed to interfere with correct dimer formation. The structure reported here is a valid template also for the dimeric structures of beta-hexosaminidase A and S.
About this Structure
1O7A is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The X-ray crystal structure of human beta-hexosaminidase B provides new insights into Sandhoff disease., Maier T, Strater N, Schuette CG, Klingenstein R, Sandhoff K, Saenger W, J Mol Biol. 2003 May 2;328(3):669-81. PMID:12706724
Page seeded by OCA on Sun Mar 30 22:40:50 2008
