1AX8

Human obesity protein, leptin

Summary for 1AX8

• Entry DOI: 10.2210/pdb1ax8/pdb
• Descriptor: OBESITY PROTEIN (2 entities in total)
• Functional Keywords: helical cytokine, hematopoietic factor, diabetes, obesity, cytokine
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P41159
• Total number of polymer chains: 1
• Total formula weight: 15984.30

Authors

Zhang, F.,Beals, J.M.,Briggs, S.L.,Clawson, D.K.,Wery, J.-P.,Schevitz, R.W. (deposition date: 1997-10-31, release date: 1998-11-25, Last modification date: 2012-05-09)

Primary citation

Zhang, F.,Basinski, M.B.,Beals, J.M.,Briggs, S.L.,Churgay, L.M.,Clawson, D.K.,DiMarchi, R.D.,Furman, T.C.,Hale, J.E.,Hsiung, H.M.,Schoner, B.E.,Smith, D.P.,Zhang, X.Y.,Wery, J.P.,Schevitz, R.W.
Crystal structure of the obese protein leptin-E100.
Nature, 387:206-209, 1997

PubMed Abstract: 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.

PubMed: 9144295
DOI: 10.1038/387206a0

Experimental method

X-RAY DIFFRACTION (2.4 Å)