Welcome to Entry Card of Lysosomal Enzymes
Details of RareLSD ID 1001 |
| RareLSD_Id | 1001 |
| ENZYME | Alpha galactosidase A |
| GENE | GLA |
| E.C.NUMBER | 3.2.1.22 |
| FAMILY | GH27 |
| CYTOGENETICS | Xq22.1 |
| DISEASE | Fabry's Disease |
| SNP | rs104894827,rs104894828,rs104894829,rs104894830,GLA-EX4DEL,rs104894831,rs28935485,rs104894832,rs104894835,rs104894836,rs104894837,rs28935195,rs28935196,rs104894838,rs2893519,rs28935488,rs104894840,rs104894841,rs28935486,rs28935487,rs104894839,rs28935489 |
| DEPOSIT | Globotriaosylceramide (Gb3 orGL3)/ceramidetrihexoside or CTH &glycosphingolipids (galabiosylceramide) |
| REF | 704691, 19621417, 3009617,17391432 |
| TEMP (in Celsius) | 37 |
| pI | NA |
| pH | 3.75 |
| Catalytic Nucleophile | Asp170 |
| Catalytic Acid/Base | Asp231 |
| Substrate | globotriaosylceramide + H2O |
| Product | DGalalpha(1,4)DGluceramide + D-galactose |
| Structure(PDB/Phyre2_ID) | 1R46 |
| kM | 0.18 |
| DRUG | Replagal (from Shire) and Fabrazyme, 1-Deoxygalactonojirymicin (DGJ)/Amigal |
| SEQ LENGTH | 429 |
| AA SEQ | MQLRNPELHLGCALALRFLALVSWDIPGARALDNGLARTPTMGWLHWERFMCNLDCQEEPDSCISEKLFMEMAELMVSEGWKDAGYEYLCIDDCWMAPQRDSEGRLQADPQRFPHGIRQLANYVHSKGLKLGIYADVGNKTCAGFPGSFGYYDIDAQTFADWGVDLLKFDGCYCDSLENLADGYKHMSLALNRTGRSIVYSCEWPLYMWPFQKPNYTEIRQYCNHWRNFADIDDSWKSIKSILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLSWNQQVTQMALWAIMAAPLFMSNDLRHISPQAKALLQDKDVIAINQDPLGKQGYQLRQGDNFEVWERPLSGLAWAVAMINRQEIGGPRSYTIAVASLGKGVACNPACFITQLLPVKRKLGFYEWTSRLRSHINPTGTVLLQLENTMQMSLKDLL |
| MODIFICATION | N-linked Glycosylation:Asn139,Asn192,Asn215,Ubiquitination:Lys240,Lys326,Lys393 |
| INHIBITOR | 1Deoxygalactonojirymicin (DGJ)/Amigal,galactostatin bisulfite,myoinositol,N-acetylDgalactosamine,N-butyldeoxygalactonojirimycin,sodium taurocholate |
| ACTIVE SITE RESIDUE | Asp170,Asp231 |
| DISULPHIDE BRIDGES | *52-94,*56-63,*142-172,*202-223,*378-382 |
| PSEUDOGENES | NA |
| MISCELLANEOUS | Mutations leading to a complete loss of enzyme activity,residues in the interior of Alpha-galactosidase A affected,Mutations leading to an Alpha-galactosidase A protein (residual enzyme activity) tend to be found in more surface exposed residues Trp, Cys, Gln, Tyr, and Gly most commonly altered by Fabry mutations |
| PARALOGS | NAGA |
| MECHANISM | Double displacement reaction two consecutive nucleophilic attacks on anomeric carbon of the substrate leads to breakage of glycosidic linkage(overall retention of the anomer of the product) |
| INHERITANCE PATTERN | X-linked recessive |
| ORGAN AFFECTED | Kidney, Heart,Eye,Skin,Muscle,Boness,Nervous System,Lungs |
| ENZYME LOCATION | NMBH |
| UniProt ID | P06280 |