1FO2
CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE IN COMPLEX WITH 1-DEOXYMANNOJIRIMYCIN
Summary for 1FO2
| Entry DOI | 10.2210/pdb1fo2/pdb |
| Related | 1FMI 1FO3 |
| Descriptor | ALPHA1,2-MANNOSIDASE, CALCIUM ION, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | alpha-alpha7 barrel, hydrolase |
| Biological source | Homo sapiens (human) |
| Cellular location | Endoplasmic reticulum membrane; Single-pass type II membrane protein: Q9UKM7 |
| Total number of polymer chains | 1 |
| Total formula weight | 53273.35 |
| Authors | Vallee, F.,Karaveg, K.,Moremen, K.W.,Herscovics, A.,Howell, P.L. (deposition date: 2000-08-24, release date: 2001-01-17, Last modification date: 2024-10-30) |
| Primary citation | Vallee, F.,Karaveg, K.,Herscovics, A.,Moremen, K.W.,Howell, P.L. Structural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases. J.Biol.Chem., 275:41287-41298, 2000 Cited by PubMed Abstract: Endoplasmic reticulum (ER) class I alpha1,2-mannosidase (also known as ER alpha-mannosidase I) is a critical enzyme in the maturation of N-linked oligosaccharides and ER-associated degradation. Trimming of a single mannose residue acts as a signal to target misfolded glycoproteins for degradation by the proteasome. Crystal structures of the catalytic domain of human ER class I alpha1,2-mannosidase have been determined both in the presence and absence of the potent inhibitors kifunensine and 1-deoxymannojirimycin. Both inhibitors bind to the protein at the bottom of the active-site cavity, with the essential calcium ion coordinating the O-2' and O-3' hydroxyls and stabilizing the six-membered rings of both inhibitors in a (1)C(4) conformation. This is the first direct evidence of the role of the calcium ion. The lack of major conformational changes upon inhibitor binding and structural comparisons with the yeast alpha1, 2-mannosidase enzyme-product complex suggest that this class of inverting enzymes has a novel catalytic mechanism. The structures also provide insight into the specificity of this class of enzymes and provide a blueprint for the future design of novel inhibitors that prevent degradation of misfolded proteins in genetic diseases. PubMed: 10995765DOI: 10.1074/jbc.M006927200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.38 Å) |
Structure validation
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