Searching sequence space: two different approaches to dihydrofolate reductase catalysis.
There are numerous examples of proteins that catalyze the same reaction while possessing different structures. This review focuses on two dihydrofolate reductases (DHFRs) that have disparate structures and discusses how the catalytic strategies of these two DHFRs are driven by their respective scaffolds. The two proteins are E. coli chromosomal DHFR (Ec DHFR) and a type II R-plasmid-encoded DHFR, typified by R67 DHFR. The former has been described as a very well evolved enzyme with an efficiency of 0.15, while the latter has been suggested to be a model for a "primitive" enzyme that has not yet been optimized by evolution. This comparison underlines what is important to catalysis in these two enzymes and concurrently highlights fundamental issues in enzyme catalysis.
Howell
Elizabeth E
EE
Department of Biochemistry, Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996-0840, USA. lzh@utk.edu
D001665:Binding Sites / Q000235:genetics; D002384:Catalysis; D020134:Catalytic Domain / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology*; D005492:Folic Acid / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009249:NADP / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D011487:Protein Conformation; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics
D008024:Ligands; D009249:NADP; D005492:Folic Acid; C098921:dihydrofolate reductase type II; D013762:Tetrahydrofolate Dehydrogenase