Convergent Evolution Of Similar Function In 2 Structurally Divergent Enzymes

AN example of two related enzymes that catalyse similar reactions but possess different active sites is provided by comparing the structure of Escherichia coli thioredoxin reductase with glutathione reductase 1. Both are dimeric enzymes that catalyse the reduction of disulphides by pyridine nucleotides through an enzyme disulphide and a flavin 2. Human glutathione reductase contains four structural domains within each molecule: the flavin-adenine dinucleotide (FAD)- and nicotinamide-adenine dinucleotide phosphate (NADPH)-binding domains, the 'central' domain and the C-terminal domain that provides the dimer interface and part of the active site 3,4. Although both enzymes share the same catalytic mechanism and similar tertiary structures, their active sites do not resemble each other 5,6. We have determined the crystal structure of E. coli thioredoxin reductase at 2 angstrom resolution, and show that thioredoxin reductase lacks the domain that provides the dimer interface in glutathione reductase, and forms a completely different dimeric structure. The catalytically active disulphides are located in different domains on opposite sides of the flavin ring system. This suggests that these enzymes diverged from an ancestral nucleotide-binding protein and acquired their disulphide reductase activities independently.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62805/1/352172a0.pd

Structure of Tumour Necrosis Factor.

Tumour necrosis factor is a trimeric molecule, each subunit of which consists of an antiparallel beta-sandwich. Individual subunits from the trimer by a novel edge-to-face packing of beta-sheets. A comparison of the subunit fold with that of other proteins reveals a remarkable similarity to the 'jelly-roll' structural motif characteristic of viral coat proteins