9GTC
Crystal structure of human lysosomal acid-alpha-glucosidase, GAA, in complex with iminosugar compound 4g
This is a non-PDB format compatible entry.
Summary for 9GTC
| Entry DOI | 10.2210/pdb9gtc/pdb |
| Related | 9GSV 9GSW |
| Descriptor | Lysosomal alpha-glucosidase, 1,2-ETHANEDIOL, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total) |
| Functional Keywords | acid-alpha-glucosidase, lysosomal, iminosugar, pompe disease, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 110138.77 |
| Authors | Sulzenbacher, G.,Roig-Zamboni, V.,Moracci, M.,Parenti, G.,Py, S. (deposition date: 2024-09-17, release date: 2025-10-01, Last modification date: 2025-10-08) |
| Primary citation | Vieira Da Cruz, A.,Perraudin, V.,Minopoli, N.,Iacono, R.,Roig-Zamboni, V.,Bossio, A.,Tangara, S.,Fayolle, M.,Kanazawa, A.,Philouze, C.,Tarallo, A.,Heming, J.J.A.,Artola, M.,Behr, J.B.,Overkleeft, H.S.,Moracci, M.,Sulzenbacher, G.,Parenti, G.,Py, S. C -Branched Iminosugars as Selective Pharmacological Chaperones of Lysosomal alpha-Glucosidase for the Treatment of Pompe Disease. J.Med.Chem., 68:19269-19286, 2025 Cited by PubMed Abstract: We report herein the design and synthesis of a series of 5--alkyldeoxynojirimycins from l-sorbose, through an efficient and scalable method amenable to preparing a large variety of analogues. The interaction of this class of compounds with human acid α-glucosidase (GAA), the genetically defective enzyme in patients suffering from Pompe disease, was investigated to identify pharmacological chaperones exhibiting high selectivity for this enzyme. Crystallographic analyses provided a rationale for their binding mode to GAA and chaperone activity. The effects of 5--phenethyl-DNJ () were evaluated on GAA activity enhancement in cells from Pompe disease patients and in GAA-KO mice. The significant increase of GAA activity in the presence of in various tissues, particularly in the diaphragm, encourages further studies on this class of small molecules toward developing clinical drugs. Their chaperone activity and excellent selectivity may offer potential benefits over the current treatments for Pompe disease. PubMed: 40951993DOI: 10.1021/acs.jmedchem.5c01349 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.58 Å) |
Structure validation
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