Premium
Homology modelling and 1 H NMR studies of human leukaemia inhibitory factor
Author(s) -
Smith David K.,
Treutlein Herbert R.,
Maurer Till,
Owczarek Catherine M.,
Layton Meredith J.,
Nicola Nicos A.,
Norton Raymond S.
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)00785-3
Subject(s) - histidine , chemistry , molecular dynamics , stereochemistry , nuclear magnetic resonance spectroscopy , molecular model , amino acid , homology modeling , mutagenesis , mutant , biochemistry , computational chemistry , enzyme , gene
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 1 H NMR data on the ionization behaviour of the six histidine residues in LIF, the imidazolium p K a values of which range from 3.6 to 7.4. These p K 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.