Amino-acid sequence of dihydrofolate reductase from a methotrexate-resistant mutant of Streptococcus faecium and identification of methionine residues at the inhibitor binding site.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 71 ·No. 8 ·1974-08-00 ·Pages 3001-5

Gleisner JM, Peterson DL, Blakley RL

Abstract

The amino-acid sequence of dihydrofolate reductase (7,8-dihydrofolate:NADP(+) oxidoreductase, EC 1.5.1.4) from S. faecium var Durans strain A is reported, and methionine residues 28 and 50 are shown to be protected by the inhibitor aminopterin from carboxymethylation by iodoacetate which occurs in absence of the inhibitor. Comparison of the sequence with that of the Escherichia coli reductase reveals two domains of considerable homology, one (the N-terminal region) presumably concerned with dihydrofolate and inhibitor binding and the other with dinucleotide binding. No significant sequence homology was found between larger dehydrogenases and the dihydrofolate reductases, which must, therefore, have evolved from a different ancestral protein.

MeSH Terms

Amino Acid Sequence Aminopterin/pharmacology Binding Sites Carbon Radioisotopes Drug Resistance, Microbial Escherichia coli/enzymology Iodoacetates/metabolism Methionine/isolation & purification Methotrexate/pharmacology Mutation Streptococcus/drug effects,enzymology Tetrahydrofolate Dehydrogenase/analysis

Chemicals

Carbon Radioisotopes Iodoacetates Methionine Tetrahydrofolate Dehydrogenase Aminopterin Methotrexate

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Gleisner J M

Peterson D L

Blakley R L

References (19)

19 references, click to expand

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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.71.8.3001

Published

1974-08-00

Pages

3001-5

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC388607

Subset

External Links

PubMed source DOI: 10.1073/pnas.71.8.3001 PMC Full Text View journal details

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Amino-acid sequence of dihydrofolate reductase from a methotrexate-resistant mutant of Streptococcus faecium and identification of methionine residues at the inhibitor binding site.

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