Crystal Structure of the Catalytic Domain of the Human Cell Cycle Control Phosphatase, Cdc25A
1998; Cell Press; Volume: 93; Issue: 4 Linguagem: Inglês
10.1016/s0092-8674(00)81190-3
ISSN1097-4172
AutoresEric B. Fauman, John Cogswell, Brett Lovejoy, Warren J. Rocque, William D. Holmes, Valerie G. Montana, Helen Piwnica‐Worms, Martin J. Rink, Mark A. Saper,
Tópico(s)Bioactive Compounds and Antitumor Agents
ResumoCdc25 phosphatases activate the cell division kinases throughout the cell cycle. The 2.3 A structure of the human Cdc25A catalytic domain reveals a small alpha/beta domain with a fold unlike previously described phosphatase structures but identical to rhodanese, a sulfur-transfer protein. Only the active-site loop, containing the Cys-(X)5-Arg motif, shows similarity to the tyrosine phosphatases. In some crystals, the catalytic Cys-430 forms a disulfide bond with the invariant Cys-384, suggesting that Cdc25 may be self-inhibited during oxidative stress. Asp-383, previously proposed to be the general acid, instead serves a structural role, forming a conserved buried salt-bridge. We propose that Glu-431 may act as a general acid. Structure-based alignments suggest that the noncatalytic domain of the MAP kinase phosphatases will share this topology, as will ACR2, a eukaryotic arsenical resistance protein.
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