Abstract
Protein kinase Cs (PKCs) are a ubiquitous family of regulatory enzymes that associate with membranes and are activated by diacylglycerol or tumor-promoting agonists such as phorbol esters. The structure of the second activator-binding domain of PKC delta has been determined in complex with phorbol 13-acetate, which binds in a groove between two pulled-apart beta strands at the tip of the domain. The C3, C4, and C20 phorbol oxygens form hydrogen bonds with main-chain groups whose orientation is controlled by a set of highly conserved residues. Phorbol binding caps the groove and forms a contiguous hydrophobic surface covering one-third of the domain, explaining how the activator promotes insertion of PKC into membranes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Crystallography
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Electrochemistry
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Enzyme Activation
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Humans
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Hydrogen Bonding
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In Vitro Techniques
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Isoenzymes / chemistry*
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Macromolecular Substances
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Membranes / chemistry
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Membranes / enzymology
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Mice
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Models, Molecular
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Molecular Sequence Data
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Molecular Structure
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Phorbol Esters / chemistry
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Phorbol Esters / metabolism
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Protein Conformation
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Protein Kinase C / chemistry*
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Protein Kinase C / genetics
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Protein Kinase C / metabolism
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Protein Kinase C-delta
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Sequence Homology, Amino Acid
Substances
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Isoenzymes
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Macromolecular Substances
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Phorbol Esters
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Prkcd protein, mouse
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PRKCD protein, human
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Protein Kinase C
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Protein Kinase C-delta