2BCD

X-ray crystal structure of Protein Phosphatase-1 with the marine toxin motuporin bound

Summary for 2BCD

• Entry DOI: 10.2210/pdb2bcd/pdb
• Related: 2BDX
• Related PRD ID: PRD_000213
• Descriptor: Serine/threonine protein phosphatase PP1-gamma catalytic subunit, MOTUPORIN, BETA-MERCAPTOETHANOL, ... (5 entities in total)
• Functional Keywords: protein phosphtase, natural product inhibitors, motuporin, nodularin, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P36873
• Total number of polymer chains: 2
• Total formula weight: 38412.47

Authors

Maynes, J.T.,Luu, H.A.,Cherney, M.M.,Andersen, R.J.,Williams, D.,Holmes, C.F.,James, M.N. (deposition date: 2005-10-19, release date: 2006-01-17, Last modification date: 2023-11-15)

Primary citation

Maynes, J.T.,Luu, H.A.,Cherney, M.M.,Andersen, R.J.,Williams, D.,Holmes, C.F.,James, M.N.
Crystal Structures of Protein Phosphatase-1 Bound to Motuporin and Dihydromicrocystin-LA: Elucidation of the Mechanism of Enzyme Inhibition by Cyanobacterial Toxins.
J.Mol.Biol., 356:111-120, 2006

PubMed Abstract: The microcystins and nodularins are tumour promoting hepatotoxins that are responsible for global adverse human health effects and wildlife fatalities in countries where drinking water supplies contain cyanobacteria. The toxins function by inhibiting broad specificity Ser/Thr protein phosphatases in the host cells, thereby disrupting signal transduction pathways. A previous crystal structure of a microcystin bound to the catalytic subunit of protein phosphatase-1 (PP-1c) showed distinct changes in the active site region when compared with protein phosphatase-1 structures bound to other toxins. We have elucidated the crystal structures of the cyanotoxins, motuporin (nodularin-V) and dihydromicrocystin-LA bound to human protein phosphatase-1c (gamma isoform). The atomic structures of these complexes reveal the structural basis for inhibition of protein phosphatases by these toxins. Comparisons of the structures of the cyanobacterial toxin:phosphatase complexes explain the biochemical mechanism by which microcystins but not nodularins permanently modify their protein phosphatase targets by covalent addition to an active site cysteine residue.

PubMed: 16343532
DOI: 10.1016/j.jmb.2005.11.019

Experimental method

X-RAY DIFFRACTION (2.1 Å)