Substrate-binding site, flexibility

In cases where there is more than one subunit per asymmetric unit, the lattice contacts may lead to asymmetric binding. In crystals of chicken triose phosphate isomerase, which contain one dimer per asymmetric unit, only one subunit was found to bind stubstrate but there was no half-sites reactivity observed in solution studies. In crystals of the yeast enzyme, where the lattice contacts are different, both subunits bind substrate and undergo substantial conformational change [161]. In both crystal forms there is a loop of chain, residues 168-177, which, in the native enzyme, exhibits conformational flexibility. On binding substrate the loop moves to close the substrate binding site and becomes ordered [223]. In the crystals of the chicken enzyme, movement of this loop for one subunit is blocked by lattice contacts. In the other subunit, movement of the loop and substrate binding are observed, just as in the yeast triose phosphate isomerase crystals. 

Fig. 2 BACE-1 characteristics. The overall fold of BACE-1 is typical for an aspartic acid protease, consisting of an N- and C-terminal lobe with the substrate binding site located in a crevice between the two lobes [99, 100], A flexible hairpin, called the flap (Yellow see-through surface), partially covers the active site of BACE-1 and can adopt many different conformations as a result of inhibitor binding. In the center of the active site are the two aspartic acid residues orange and inset) that are involved in the enzymatic reaction... 

It Is argued that volume is a better measure of sterlo effects for a flexible look receptor than are 1/or Es Alternatively, It has been suggested that bulk parameters are actually a measure of polarlzablli ty and represent London(dlsperslon)forces In substrate receptor site binding. 

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