Phospholipid bound to the flavohemoprotein from Alcaligenes eutrophus

The structurally characterized flavohemoprotein from Alcaligenes eutrophus (FHP) contains a phospholipid-binding site with 1-16 : 0-2-cyclo-17: 0-diac yl-glycerophospho-ethanolamine and 1-16 : 0-2-cyclo-17 : 0-diacyl-glyceroph ospho-glycerol as the major occupying compounds. The structure of the phosp holipid is characterized by its compact form, due to the -sc/beta/-sc confo rmation of the glycerol and the nonlinear arrangement of the sn-1- and sn-2 -fatty acid chains. The phospholipid-binding site is located adjacent to th e heme molecule at the bottom of a large cavity. The fatty acid chains form a large number of van der Waal's contacts with nonpolar side chains, where as the glycerophosphate moiety, which points towards the entrance of the ch annel, is linked to the protein matrix by polar interactions. The thermodyn amically stable globin module of FHP, obtained after cleaving off the oxido reductase module, also contains the phospholipid and can therefore be consi dered as a phospholipid-binding protein. Single amino acid exchanges design ed to decrease the lipid-binding site revealed both the possibility of bloc king incorporation of the phospholipid and its capability to evade steric b arriers. Conformational changes in the phospholipid can also be induced by binding heme-ligating compounds. Phospholipid binding is not a general feat ure of flavohemoproteins, because the Escherichia coli and the yeast protei n exhibit less and no lipid affinity, respectively.