1TRB

CONVERGENT EVOLUTION OF SIMILAR FUNCTION IN TWO STRUCTURALLY DIVERGENT ENZYMES

Summary for 1TRB

• Entry DOI: 10.2210/pdb1trb/pdb
• Descriptor: THIOREDOXIN REDUCTASE, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: oxidoreductase(flavoenzyme)
• Biological source: Escherichia coli
• Cellular location: Cytoplasm: P0A9P4
• Total number of polymer chains: 1
• Total formula weight: 35299.25

Authors

Kuriyan, J.,Krishna, T.S.R. (deposition date: 1991-09-07, release date: 1994-01-31, Last modification date: 2024-02-14)

Primary citation

Kuriyan, J.,Krishna, T.S.,Wong, L.,Guenther, B.,Pahler, A.,Williams Jr., C.H.,Model, P.
Convergent evolution of similar function in two structurally divergent enzymes.
Nature, 352:172-174, 1991

PubMed Abstract: 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. Both are dimeric enzymes that catalyse the reduction of disulphides by pyridine nucleotides through an enzyme disulphide and a flavin. 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. Although both enzymes share the same catalytic mechanism and similar tertiary structures, their active sites do not resemble each other. We have determined the crystal structure of E. coli thioredoxin reductase at 2 A 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.

PubMed: 2067578
DOI: 10.1038/352172a0

Experimental method

X-RAY DIFFRACTION (2 Å)