Protein engineering reveals ancient adaptive replacements in isocitrate dehydrogenase.
Proc Natl Acad Sci U S A
; 94(7): 3104-9, 1997 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-9096353
ABSTRACT
Evolutionary analysis indicates that eubacterial NADP-dependent isocitrate dehydrogenases (EC 1.1.1.42) first evolved from an NAD-dependent precursor about 3.5 billion years ago. Selection in favor of utilizing NADP was probably a result of niche expansion during growth on acetate, where isocitrate dehydrogenase provides 90% of the NADPH necessary for biosynthesis. Amino acids responsible for differing coenzyme specificities were identified from x-ray crystallographic structures of Escherichia coli isocitrate dehydrogenase and the distantly related Thermus thermophilus NAD-dependent isopropylmalate dehydrogenase. Site-directed mutagenesis at sites lining the coenzyme binding pockets has been used to invert the coenzyme specificities of both enzymes. Reconstructed ancestral sequences indicate that these replacements are ancestral. Hence the adaptive history of molecular evolution is amenable to experimental investigation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Engineering
/
Isocitrate Dehydrogenase
Type of study:
Prognostic_studies
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
1997
Document type:
Article
Affiliation country:
United States