Human aldolase B: liver-specific properties of the isozyme depend on type B isozyme group-specific sequences

A series of chimeric enzymes between two human aldolases A,B or C were constructed to identify the molecular regions responsiblefor isozyme-specific functions. Chimeras constructed betweenaldolases A and B were AB34 (an AB chimera connected at position34), ABA34–306 and ABA212–306 (the ABA chimeras).Those between aldolases B and C are BC243, BC263 and BC306 (theBC chimeras connected at positions as indicated), as well asCB55, CB243, CB263 and CB306 (the CB chimeras connected at positionsas indicated), CBC55–263 (a CBC chimera), and BCB55–193,BCB55–306, BCB79–193 and BCB79–306 (the BCBchimeric enzymes). Through the analysis of the properties ofthese chimeras, it was found that for aldolase B, isozyme Bgroup-specific sequences (IGSs)-l and-4 were required for exertingtype B-specific functions, while the IGSs-2 and -3 enhanced,in collaboration with the IGS-1, the catalytic activity of aldolaseB. In addition, the /ß-barrel and the restricted stretches,which were not specified but occupied two distinct regions spanningthe amino acid positions 108–137 (designated connector1) and 243–306 (designated connector 2), were found tobe indispensable for showing full catalytic activity of aldolaseB.