Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester.
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.
Zhang
G
G
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0580, USA.
Kazanietz
M G
MG
Blumberg
P M
PM
Hurley
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003461:Crystallography; D004563:Electrochemistry; D004789:Enzyme Activation; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances; D008566:Membranes / Q000737:chemistry / Q000201:enzymology; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010703:Phorbol Esters / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011493:Protein Kinase C / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051745:Protein Kinase C-delta; D017386:Sequence Homology, Amino Acid
D007527:Isoenzymes; D046911:Macromolecular Substances; D010703:Phorbol Esters; C497259:Prkcd protein, mouse; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta