What function for human lithostathine?: structural investigations by three-dimensional structure modeling and high-resolution NMR spectroscopy

Human lithostathine is a 144-residue protein, expressed in variousorgans and pathologies. Several biological functions have beenproposed for this protein. Among others, inhibition of nucleationand growth of CaCO₃ crystals in the pancreas and bacterial aggregationhas retained attention, because lithostathine presents highsequence similarities with calcium-dependent (or C-type) lectins.To study its structure-function relationship and compare itwith that of C-type lectins, we have built a model for lithostathine.This model is derived from the only two C-type lectins of knownstructures: rat mannose binding protein and human E-selectin.An original strategy, inspired by that proposed by Havel andSnow, was designed for model building. We have undertaken NMRstudies on the natural protein. Although complete structuredetermination has not yet been achieved, the NMR studies didconfirm the main characteristics of the model. From analysisof the proposed model, we concluded that lithostathine is notexpected to present sugar- or calcium-binding properties. Therefore,the mechanisms of bacterial aggregation and inhibition of CaCO₃nucleation and growth have not yet been elucidated.