1ax8: Difference between revisions
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==Overview== | ==Overview== | ||
Mutations in the obese gene (OB) or in the gene encoding the OB | 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 phenotypes. The demonstration that OB protein (also known as leptin) can normalize body weight in ob/ob mice has generated enormous interest. 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 (CNS). Injection of leptin into the CNS of overfed rodents resistant to peripheral administration was found to induce biological activity. Consequently, for the leptin to act as a weight-lowering hormone in human obesity, it appears that appropriate concentrations must be present in the CNS. This places a premium on understanding the structure of the hormone in order to design more potent and selective agonists. Here we report the crystal structure at 2.4A resolution of a human mutant OB protein (leptin-E100) that has comparable biological activity to wild type but which crystallizes more readily. The structure reveals a four-helix bundle similar to that of the long-chain helical cytokine family. | ||
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Beals, J | [[Category: Beals, J M.]] | ||
[[Category: Briggs, S | [[Category: Briggs, S L.]] | ||
[[Category: Clawson, D | [[Category: Clawson, D K.]] | ||
[[Category: Schevitz, R | [[Category: Schevitz, R W.]] | ||
[[Category: Wery, J | [[Category: Wery, J P.]] | ||
[[Category: Zhang, F.]] | [[Category: Zhang, F.]] | ||
[[Category: diabetes]] | [[Category: diabetes]] | ||
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[[Category: obesity]] | [[Category: obesity]] | ||
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Revision as of 12:49, 21 February 2008
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HUMAN OBESITY PROTEIN, LEPTIN
OverviewOverview
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 phenotypes. The demonstration that OB protein (also known as leptin) can normalize body weight in ob/ob mice has generated enormous interest. 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 (CNS). Injection of leptin into the CNS of overfed rodents resistant to peripheral administration was found to induce biological activity. Consequently, for the leptin to act as a weight-lowering hormone in human obesity, it appears that appropriate concentrations must be present in the CNS. This places a premium on understanding the structure of the hormone in order to design more potent and selective agonists. Here we report the crystal structure at 2.4A resolution of a human mutant OB protein (leptin-E100) that has comparable biological activity to wild type but which crystallizes more readily. The structure reveals a four-helix bundle similar to that of the long-chain helical cytokine family.
DiseaseDisease
Known diseases associated with this structure: Obesity, morbid, with hypogonadism OMIM:[164160], Obesity, severe, due to leptin deficiency OMIM:[164160]
About this StructureAbout this Structure
1AX8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the obese protein leptin-E100., Zhang F, Basinski MB, Beals JM, Briggs SL, Churgay LM, Clawson DK, DiMarchi RD, Furman TC, Hale JE, Hsiung HM, Schoner BE, Smith DP, Zhang XY, Wery JP, Schevitz RW, Nature. 1997 May 8;387(6629):206-9. PMID:9144295
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