Chemical Ecology The Chemistry of Biotic Interaction (1995) / Chapter Skim
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The Chemistry of Signal Transduction
The Chemistry of Signal Transduction
Pages 133-146
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From page 133... ...
The Chemistry of Sexual Selection /129 They attack both pupae and eggs, and they appear to be driven to cannibalism not so much by hunger as by the PA deficiency itself. Moreover, they target specifically eggs and pupae that are PA-laden rather than PA-free.
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From page 134... ...
130 / Thomas Eisner and Jerrold Meinwald The closest parallel to the Utetheisa strategy is exhibited by danaine butterflies (family Nymphalidae)
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(1972) in Phytochemical Ecology, ed.
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132 / Thomas Eisner and Jerrold Meinwald 26. LaMunyon, C
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(i) When an external molecule stimulates the IgE receptor on the surface of a mast cell, an intracellular signal leads to the release of histamine in a process referred to as degranulation (21.
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, FK506, and rapamycin are all microbial natural products that are probably synthesized to chemically defend their producing organism (5~. Studying these natural products as microbial chemical warfare agents would unarguably qualify as chemical ecology.
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From page 139... ...
It was isolated from Streptomyces hygroscopicus from Easter Island, and the name rapamycin comes from Rapa Nui, the native name for Easter Island. All three agents have a variety of biological effects, but early studies showed that they interfere with a cytosolic signaling step and thus could be used to probe the cytoplasmic signal transduction pathway.
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IMMUNOPHILINS AND TEIEIR COMPLEXES The inhibitory natural products were used to identify their cellular targets, and in each case a hiahlv specific binding protein was identified.
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From page 141... ...
the yeast Saccharomyces cerevisiae, normally sensitive to FK506 and CsA, remains viable and insensitive to either drug when FKBP or CyPA is knocked out chemically or genetically (25, 261. In the currently accepted model, the complex of the immunosuppressive agent with its cognate protein inhibits cytoplasmic signal transduction (61.
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From page 142... ...
Both NMR and x-ray structural studies on FKBP12 and its complexes show that the protein folds as a five-stranded ,B-sheet wrapped around a short oc-helix with an overall shape resembling an ice cream cone (Figure 2 Left)
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The Chemistry of Signal Transduction Ace, FIGURE 2 (Left) Diagram of the FKBP12-FK506 complex.
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From page 144... ...
Jon Clardy FKS06 ~` FK506 H/A87 `,,c~ ~8 Y^'6 ~ ' ,~ ,~ -_, ~` ,, ~`> IJK90 9 F99 '~636 -~~ ~ r'` H/A87 W59 %~,~ P88 Y26: I" F99 r~ F36 .Yd'2~,.' Amp FIGURE 3 A stereo view of the FKBP-FK506 binding region. The FKBP13 structure is shown with solid (yellow)
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From page 145... ...
However, the single amino acid change Arg-42 to glutamine in FKBP12 diminishes calcineurin inhibition by 2 orders of magnitude. A recently completed x-ray analysis of the FKBP13-FK506 complex adds a detailed structural understanding to these mutational results (441.
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From page 146... ...
The hybrid ligands were developed around the o`-keto homoprolyl moiety found in FK506 an element that appears crucial for tight binding. The adjoining amino acids were optimized to give maximum binding, and finally the variable-length tethers were added (Figure 4C)
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