1AX8

Human obesity protein, leptin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.185 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystal structure of the obese protein leptin-E100.

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.

(1997) Nature 387: 206-209

  • DOI: https://doi.org/10.1038/387206a0
  • Primary Citation of Related Structures:  
    1AX8

  • 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.


  • Organizational Affiliation

    Research Technologies and Proteins, Endocrine Research Divisions, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.zhang_faming@lilly.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
OBESITY PROTEIN146Homo sapiensMutation(s): 1 
Gene Names: OBESE GENE
UniProt & NIH Common Fund Data Resources
Find proteins for P41159 (Homo sapiens)
Explore P41159 
Go to UniProtKB:  P41159
PHAROS:  P41159
GTEx:  ENSG00000174697 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP41159
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.185 
  • Space Group: P 63
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 88.14α = 90
b = 88.14β = 90
c = 48.05γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MLPHAREphasing
X-PLORrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1998-11-25
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2012-05-09
    Changes: Derived calculations