Involvement of tryptophan residues of lysozyme in its binding with cytosine arabinoside.
Cytosine-1-beta-D-arabinofuronaside, an antileukemic drug and hen egg white lysozyme (E.C. 3.2.1.17) form a 1:1 complex with Ka 1.2 X 10(4) M-1 at low drug concentrations. However, association was cooperative in nature at high concentrations with values of Ka = 1.8 X 10(4) M-1 and N = 2. Involvement of tryptophan in the drug protein complex was evident from fluorescence quenching and from the association of the drug with free tryptophan with a Ka = 1.5 X 10(4) M-1. Modification of tryptophan 108 reduced the binding by 89% suggesting a major role for this residue in the binding process. Oxidation of tryptophan 62 and acetylation of lysine residues also decreased the affinity of the drug to the protein by 55 and 66% respectively. Binding improved with increase in temperature and positive values for change in enthalpy and entropy were obtained. Ara-C inhibited lysozyme activity noncompetitively.
D003561:Cytarabine / Q000378:metabolism* / Q000494:pharmacology; D009113:Muramidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014364:Tryptophan / Q000378:metabolism*
D003561:Cytarabine; D014364:Tryptophan; D009113:Muramidase