2VC9
Family 89 Glycoside Hydrolase from Clostridium perfringens in complex with 2-acetamido-1,2-dideoxynojirmycin
Summary for 2VC9
Entry DOI | 10.2210/pdb2vc9/pdb |
Related | 2VCA 2VCB 2VCC |
Descriptor | ALPHA-N-ACETYLGLUCOSAMINIDASE, 2-ACETAMIDO-1,2-DIDEOXYNOJIRMYCIN, GLYCEROL, ... (5 entities in total) |
Functional Keywords | mucopolysaccharidosis, 2-acetamido-1, 2-dideoxynojirmycin, gh89, naglu, sanfilippo disease, hydrolase, alpha-n-acetylglucosaminidase, family 89 glycoside hydrolase |
Biological source | CLOSTRIDIUM PERFRINGENS |
Total number of polymer chains | 1 |
Total formula weight | 102701.71 |
Authors | Ficko-Blean, E.,Stubbs, K.A.,Berg, O.,Vocadlo, D.J.,Boraston, A.B. (deposition date: 2007-09-19, release date: 2008-03-18, Last modification date: 2024-05-08) |
Primary citation | Ficko-Blean, E.,Stubbs, K.A.,Nemirovsky, O.,Vocadlo, D.J.,Boraston, A.B. Structural and Mechanistic Insight Into the Basis of Mucopolysaccharidosis Iiib. Proc.Natl.Acad.Sci.USA, 105:6560-, 2008 Cited by PubMed Abstract: Mucopolysaccharidosis III (MPS III) has four forms (A-D) that result from buildup of an improperly degraded glycosaminoglycan in lysosomes. MPS IIIB is attributable to the decreased activity of a lysosomal alpha-N-acetylglucosaminidase (NAGLU). Here, we describe the structure, catalytic mechanism, and inhibition of CpGH89 from Clostridium perfringens, a close bacterial homolog of NAGLU. The structure enables the generation of a homology model of NAGLU, an enzyme that has resisted structural studies despite having been studied for >20 years. This model reveals which mutations giving rise to MPS IIIB map to the active site and which map to regions distant from the active site. The identification of potent inhibitors of CpGH89 and the structures of these inhibitors in complex with the enzyme suggest small-molecule candidates for use as chemical chaperones. These studies therefore illuminate the genetic basis of MPS IIIB, provide a clear biochemical rationale for the necessary sequential action of heparan-degrading enzymes, and open the door to the design and optimization of chemical chaperones for treating MPS IIIB. PubMed: 18443291DOI: 10.1073/PNAS.0711491105 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.36 Å) |
Structure validation
Download full validation report