3DX2

Golgi mannosidase II complex with MANNOSTATIN B

Summary for 3DX2

• Entry DOI: 10.2210/pdb3dx2/pdb
• Related: 1HTY 1HWW 1HXK 1PS2 1QWN 1R33 1R34 1TQV 2ALW 2F7O 2F7P 2F7Q 2F7R 2FYV 3BUB 3BUP 3CZN 3DX0 3DX1 3DX3 3DX4
• Descriptor: Alpha-mannosidase 2, ZINC ION, (4R)-2-METHYLPENTANE-2,4-DIOL, ... (6 entities in total)
• Functional Keywords: gh38 glycosidase, glycosidase, golgi apparatus, hydrolase, membrane, metal-binding, signal-anchor, transmembrane, zinc
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 1
• Total formula weight: 120316.78

Authors

Kuntz, D.A.,Zhong, W.,Guo, J.,Rose, D.R.,Boons, G.-J. (deposition date: 2008-07-23, release date: 2009-07-07, Last modification date: 2023-08-30)

Primary citation

Kuntz, D.A.,Zhong, W.,Guo, J.,Rose, D.R.,Boons, G.J.
The molecular basis of inhibition of Golgi alpha-mannosidase II by mannostatin A.
Chembiochem, 10:268-277, 2009

PubMed Abstract: Mannostatin A is a potent inhibitor of the mannose-trimming enzyme, Golgi alpha-mannosidase II (GMII), which acts late in the N-glycan processing pathway. Inhibition of this enzyme provides a route to blocking the transformation-associated changes in cancer cell surface oligosaccharide structures. Here, we report on the synthesis of new Mannostatin derivatives and analyze their binding in the active site of Drosophila GMII by X-ray crystallography. The results indicate that the interaction with the backbone carbonyl of Arg876 is crucial to the high potency of the inhibitor-an effect enhanced by the hydrophobic interaction between the thiomethyl group and an aromatic pocket vicinal to the cleavage site. The various structures indicate that differences in the hydration of protein-ligand complexes are also important determinants of plasticity as well as selectivity of inhibitor binding.

PubMed: 19101978
DOI: 10.1002/cbic.200800538

Experimental method

X-RAY DIFFRACTION (1.4 Å)