PROCESSES UNDERLYING INTERACTIONS OF HUMAN LACTOFERRIN WITH THE JURKAT HUMAN LYMPHOBLASTIC T-CELL LINE RECEPTOR .2. COMPARATIVE MOLECULAR-FIELD ANALYSIS

It has previously been established that all or part of residues 4-52 o f human lactoferrin interact with the specific T-lymphocyte receptor. Furthermore, the preliminary study using classical quantitative struct ure-affinity relationships (QSAR) models have pointed out the importan ce of some H-bond donor and acceptor groups of aminoacids in the inter actions. In the present paper, comparative molecular field analysis (C oMFA) was used as a three-dimensional QSAR method to define major ster ic and electrostatic features of lactoferrin-T-lymphocyte interactions . According to steric interaction energies, some residues of human lac toferrin: R3, F20, Q23, R24, S38 and Q47, previously described by the QSAR method, as well as Q21, R27 and R56 look essential for interactio ns. The results of the electrostatic features study are also in good a greement with the QSAR H-bonds model and demonstrate that the pHi is a significant binding factor. Taken as a whole, QSAR and CoMFA methods allow to define two regions, potentially involved in selectivity betwe en species, R3, Q7, N13, Q23, R24, S38, Q50 and N55; and binding poten cy, P14, F20, D43, S44, P45 and Q47.