Main structural and functional features of the basic cytosolic bovine 21 kDa protein delineated through Hydrophobic Cluster Analysis and molecular modelling

A 21 kDa protein purified from bovine brain cytosol was previouslydescribed as a hydrophobic ngand binding protein; however, itsaccurate biological function remained still uncertain. In orderto get further information about its potential biological role,an extended prediction of its secondary and three dimensionalstructures was undertaken. We describe here a process whichpermitted us to discover a structural homology between the 21kDa protein and the N-domain of yeast phosphoglycerate kinase(PGK). This process is based on comparing the 21 kDa proteinwith all the proteins presenting a slight homology, by usingthe Hydrophobic Cluster Analysis (HCA) method. According tothe observed similarity between the N-domaln of yeast PGK andthe 21 kDa protein, we built a model which was shown to possessa potential binding site for nucleotides. Moreover, the modelobtained presents three-dimensional (3D) structure similaritywith adenylate kinase. These results suggest two main hypotheses:(0 the 21 kDa protein may belong to the kinase family; (ii)the binding of a nucleotide could imply a modification of the3D structure of the 21 kDa protein that can promote the transferof hydrophobic ligands to the plasma membrane. Meanwhile, verificationof these hypotheses has been in part performed experimentally:the 21 kDa protein binds MgATP as well as, to a lesser extent,phosphoglycerate.