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PMID: 9096353 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Protein engineering reveals ancient adaptive replacements in isocitrate dehydrogenase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 7 ·1997-04-01 ·Pages 3104-9

Dean AM, Golding GB

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.

MeSH Terms
Amino Acid Sequence Isocitrate Dehydrogenase/genetics,metabolism Molecular Sequence Data NADP/metabolism Phylogeny Protein Engineering Sequence Homology, Amino Acid Substrate Specificity
Chemicals
NADP Isocitrate Dehydrogenase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Dean A M
Department of Biological Chemistry, The Chicago Medical School, North Chicago, IL 60064-3095, USA.
Golding G B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.7.3104
Published
1997-04-01
Pages
3104-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC20329
Subset
IM
Grants
NIGMS NIH HHS · GM-48735 · United States
External Links
PubMed source DOI: 10.1073/pnas.94.7.3104 PMC Full Text View journal details
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