HOMOLOGY MODELING AND H-1-NMR STUDIES OF HUMAN LEUKEMIA INHIBITORY FACTOR
- Author(s)
- Smith, DK; Treutlein, HR; Maurer, T; Owczarek, CM; Layton, MJ; Nicola, NA; Norton, RS;
- Details
- Publication Year 1994-08-22,Volume 350,Issue #2-3,Page 275-280
- Journal Title
- FEBS LETTERS
- Publication Type
- Journal Article
- Abstract
- Human leukaemia inhibitory factor (LIF) is a glycoprotein with a diverse range of activities on many cell types. A molecular model of LIF has been constructed based mainly on the structure of the related cytokine granulocyte colony-stimulating factor, and refined using simulated annealing and molecular dynamics in water. The model was stable during molecular dynamics refinement and is consistent with known stereochemical data on proteins. It has been assessed by comparison with H-1 NMR data on the ionization behaviour of the six histidine residues in LIF, the imidazolium pK(a) values of which range from 3.6 to 7.4. These pK(a) values were assigned to individual histidine residues from NMR studies on a series of His --> Ala mutants. The environments of the histidine residues in the model account very well for their observed ionization behaviour. Furthermore, the model is consistent with mutagenesis studies which have defined a group of amino acid residues involved in receptor binding.
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- COLONY-STIMULATING FACTOR; ONCOSTATIN-M; CRYSTAL-STRUCTURE; GROWTH-HORMONE; PROTEIN; SPECTROSCOPY; RECEPTOR; ALIGNMENT; BARNASE; PATTERN
- Publisher's Version
- https://doi.org/10.1016/0014-5793(94)00785-3
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1994-08-22 12:00:00