Crystal structure of the obese protein Ieptin-E100

@article{Zhang1997CrystalSO,
  title={Crystal structure of the obese protein Ieptin-E100},
  author={Faming Zhang and M. Basinski and John Michael Beals and Stephen L. Briggs and Lisa M. Churgay and David Clawson and Richard D. DiMarchi and Thomas Charles Furman and John E Hale and Hansen Maxwell Hsiung and Brigitte Elisabeth Schoner and Dennis P. Smith and Xing-yue Zhang and Jean Pierre Wery and Richard Walter Schevitz},
  journal={Nature},
  year={1997},
  volume={387},
  pages={206-209}
}
Mutations in the obese gene (OB) or in the gene encoding the OB receptor(OB-R) result in obesity, infertility and diabetes in a variety of mouse phenotypes1–7. The demonstration that OB protein (also known as leptin) can normalize body weight in ob/ob mice has generated enormous interest8–11. Most human obesity does not appear to result from a mutant form of leptin: rather, serum leptin concentrations are increased and there is an apparent inability to transport it to the central nervous system… 
Structure, production and signaling of leptin.
Structure-Function Studies of Human Leptin*
TLDR
The results clearly demonstrate that the N-terminal region of leptin is essential for both its biological and receptor binding activities, and the amino acid sequence of the C-Terminal loop structure is also important for enhancing these actions, whereas the C -terminal disulfide bond is not needed.
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TLDR
Before leptin can play a role in the treatment of obesity, more studies are needed to discover which is the adequate dose, which the best route and form of administration and how the authors can select the patients who will benefit from this particular therapy.
Hyperleptinemia of Pregnancy Associated with the Appearance of a Circulating Form of the Leptin Receptor*
TLDR
It is found that the placenta produces large amounts of the OB-Re isoform of leptin receptor mRNA, which encodes a soluble binding protein, and the extreme hyperleptinemia of late pregnancy is attributable to binding of the leptin by a secreted form of the adipose cells' leptin receptor made by the Placenta.
Truncated Human Leptin (Δ133) Associated with Extreme Obesity Undergoes Proteasomal Degradation after Defective Intracellular Transport.
TLDR
The mechanisms underlying the defective secretion of the truncated leptin gene are examined in transient transfection studies in Chinese hamster ovary and monkey kidney epithelium cells and the inhibitor clastolactacystin β-lact...
Truncated human leptin (delta133) associated with extreme obesity undergoes proteasomal degradation after defective intracellular transport.
TLDR
The delta133 mutant leptin is not secreted but accumulates intracellularly, as a consequence of misfolding/aggregation, and is subsequently degraded by the proteasome.
The biology of leptin: a review.
TLDR
The profound effects of leptin on regulating body energy balance make it a prime candidate for drug therapies for humans and animals.
Uncovering the molecular mechanisms behind disease-associated leptin variants
TLDR
It is inferred that mutation-induced leptin deficiency may arise from several distinct mechanisms including (i) blockade of leptin receptor interface II, (ii) decreased affinity in the second step of leptin's interaction with its receptor, (iii) leptin destabilization, and (iv) unsuccessful threading through the covalent loop, leading to leptin misfolding/aggregation.
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RECENTLY Zhang et al.1 cloned a gene that is expressed only in adipose tissue of the mouse. The obese phenotype of theob/ob mouse is linked to a mutation in the obese gene that results in expression
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TLDR
A leptin receptor was recently cloned from choroid plexus and shown to map to the same 6-cM interval on mouse chromosome 4 as db8, suggesting that the weight-reducing effects of leptin may be mediated by signal transduction through a leptin receptor in the hypothalamus.
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TLDR
Injection of wild-type mice twice daily with the mouse protein resulted in a sustained 12 percent weight loss, decreased food intake, and a reduction of body fat from 12.2 to 0.7 percent, suggesting that the OB protein serves an endocrine function to regulate body fat stores.
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TLDR
Cloned a long isoform of the wild-type leptin receptor that is preferentially expressed in the hypothalamus and shows that it can activate signal transducers and activators of transcription (STAT)-3, STAT-5, and STAT-6, and identify three STAT proteins as potential mediators of the anti-obesity effects of leptin.
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TLDR
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TLDR
The data suggest that the OB protein regulates body weight and fat deposition through effects on metabolism and appetite.
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TLDR
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TLDR
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