Based on these results, it is concluded that the insensitivity of L. donovani to CsA is probably due to the paucity of CsA binding activity in the cytoplasm of the parasite. We suggest that LdCyP, located in the secretory pathway, may function as a chaperone by binding to membrane proteins rather than as the mediator of CN inhibition.

The state of the lipid phase of the membrane plays a key role in the exposure of various receptors, antigens and enzymes on the membrane surface. The fluidity of membranes of Leishmania donovani promastigotes was monitored by two independent methods, i.e. influx of sterol from liposomes and removal of phospholipids by treatment with phospholipase C. The altered sterol/phospholipid ratio, in both cases, provided evidence that the activity of the functionally important membrane-bound enzyme Mg2(+)-ATPase is modulated by the state of the lipid phase of the membrane.

Receptors interacting with terminal sugars as ligands are involved in the binding of Leishmania donovani promastigotes to the macrophage surface and their subsequent internalization. Mannose and glucose are specifically involved in the binding process. Decreased binding occurs to macrophages already infected with L. donovani either in vivo or in vitro. When mannose- or glucose-bearing liposomes are used as ligands the binding shows similar trends and the percentage inhibition of binding with mannose-bearing liposomes increases when compared to that for the glucose-bearing ones. The decreased binding of the ligand seems to be due to a decrease in the number of receptors after infection. The affinity of the ligands for the binding sites either on the normal macrophages or on the infected macrophages apparently remains the same. The results based on the incorporation of [3H]phenyl alanine and supported by the binding of glycosylated liposomes to both infected and non-infected macrophages suggest that protein synthesis, in general, is suppressed in L. donovani-infected macrophages thus affecting also mannose/glucose receptor protein synthesis, resulting in fewer receptors on the macrophage surface.

Cyclophilin from the parasite Leishmania donovani is a protein with peptidylprolyl cis-trans isomerase activity, in addition to being a receptor for the drug cyclosporin. Crystals of the enzyme have been obtained in space group P4(3)2(1)2, with unit-cell parameters a = b = 48.73, c = 140.93 A, and diffract to 3.5 A resolution. One molecule per asymmetric unit gives a solvent content and Matthews coefficient of 46% and 2.3 A(3) Da(-1), respectively. Molecular-replacement calculations with human cyclophilin A as the search model give an unambiguous solution in rotation and translation functions.

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