The topologies and folding conformations differ between enzymes to provide specific active sites.  Two of the enzymes are alpha/beta proteins, however, chalcone isomerase has the structure of a three-layer (beta-beta-alpha) sandwich and mandelate racemase has the structure of a TIM barrel and a two-layer sandwich.  The topology for DNA topoisomerase 1 is unknown according to CATH and SCOP.  Chalcone isomerase is made of a set of beta strands that form a large sheet with two alpha helices on the other side of the cleft.  Most of the binding of the chalcone isomerase active site is between hydrophobic residues.  There are few electrostatic interactions that occur at the hydroxy substituents and enone group.  Also Lys109 and Thr48/Tyr106 have strong electrostatic interactions in the active site.  Chalcone isomerase is found to have two active sties, A and B.  The Thr48 residue interacts by hydrogen bonding with O7 of the chalcone isomerase B site (9).  The active site also forms a (2S)-naringen-binding cleft made of a hydrogen-bonding network to bind the substrate, five water molecules and Tyr106  The cleft also has two other side chains involved in hydrogen bonding (4).  These side chains are Asn-113 and Thr190  The active site of chalcone isomerase is stabilized by hydrogen bonding, where the TIM barrel is important to the active site of mandelate racemase. 

The TIM barrel in mandelate racemase is made of an N-terminal domain ~140 residues and constructed into a ß3alpha4 sandwich.  The ß/alpha barrel domain is made of ~200 residues (10).  The N-terminal and central beta-barrel have hydrophobic amino acids which make up the domains (11).  Along with this TIM barrel there is a flexible loop that closes over the active site and is made of residues 19-30.  The interactions to construct the active site are important in protein folding. A functional and structural pseudosymmetry in the active sites that are made of a flexible hydrophobic pocket has been found.  The active site also consists of an amino group from Lys166, which acts as a general base, an imidazole group from His297, which also acts as a general base during the reverse reaction and a Lys164, Glu317 and Mg²⁺ (in green) ligand which bind by hydrogen binding (3).  Much has been studied about the topology of both chalcone isomerase and mandelate racemase compared to DNA topoisomerase 1. 

There are, however, interactions that stabilize the active site of DNA topoisomerase 1.  The enzyme attaches covalently to the 5’ end of the broken strand stabilizing the enzyme with the substrate.  Also DNA topoisomerase 1 is found to have four discrete domains.  The enzyme is bilobed and the domains are split in these two lobes.  The first domain is the N-terminal, which is highly charged but poorly conserved.  The other three domains make up the core domain.  In this domain are the cap region, linker and C-terminal domain.  The cap region is made of subdomains one and two, which is a mix of alpha helices and beta sheets.  This region also has two nose-cone helices that are found at the top of the bilobed protein.  The linker and C-terminal domain make up the core subdomain three, which is the lobe that sits below the DNA.  These are all alpha helical except one three-stranded beta sheet.  They are also composed of catalytic residues that are active in strand cleavage and regulation reactions.  The C-terminal is conserved and contains a nucleophilic Tyr723.  The linker region is positively charged and connects the C-terminal domain to the core domain.  The bilobe structure of the protein allows the structure to clamp around the DNA by phosphate interactions.  The two lobes are connected by a continuous alpha helical chain on one side and on the other side by a salt bridge (6).  Although the topology structure at the higher level seems to be similar, the more in depth the structure goes there is significant difference that shows between active sites of each enzyme.