Disease relevance of ECs2318

• Mutation of the His of this so-called B site of Escherichia coli fumarase had little effect on the overall initial rate kinetics of the enzyme, which has obscured an understanding of the critical role of the site [1].
• The nucleotide sequence of a 2.14 kb fragment of Bacillus subtilis DNA containing the citG gene encoding fumarase was determined using the dideoxy chain termination method [2].
• Some of the 56 amino acid substitutions must be responsible for the functional preferences of the enzymes for malate dehydration (FUMB) and fumarate hydration (FUMA) [3].
• The weakly complementing class of transducing phages, lambda fumB, contained several genes in an 8.2-kilobase HindIII fragment, including one (fumB) that determines a minor fumarase activity [4].
• The N-terminal amino acid sequence showed similarity to the sequences of fumarase A and B of Escherichia coli (56%) and fumarase A of Salmonella typhimurium (63%) [5].

High impact information on ECs2318

• The role of a malate binding site in a concavity external to the more deeply situated active site has been a major mystery of the fumarase reaction [1].
• Fumarase C, the stable fumarase of Escherichia coli, is controlled by the soxRS regulon [6].
• We report in this paper that highly purified Escherichia coli dihydroxy-acid dehydratase, fumarase A, fumarase B, and mammalian aconitase are inactivated by O2- with second order rate constants in the range of 10(6) to 10(7) M-1 s-1 [7].
• These observations were made both with wild-type envelopes and with envelopes of a mutant which lacks the enzymes succinate dehydrogenase and fumarase, indicating that the switching-promoting activity of the analogues was not caused by their conversion to fumarate [8].
• Of these regions, the region of Gln96-Gly100 is proposed as a part of the recognition site of the alpha-amino group in L-aspartate for aspartase and the hydroxyl group in L-malate for fumarase [9].

Chemical compound and disease context of ECs2318

• We report here that E. coli fumarase A, fumarase B, and aconitase are also inactivated in vivo by hyperbaric O2 [7].
• Escherichia coli fumarase A catalyzes the isomerization of enol and keto oxalacetic acid [10].
• The level of fumarase activity in Bacillus subtilis depends on the nutritional environment; in rich medium low vegetative levels increase towards the end of the exponential phase, whereas in minimal glucose medium levels are relatively high throughout growth [11].

Biological context of ECs2318

• A tungstate derivative used in the X-ray analysis is a competitive inhibitor and places the active site of fumarase in a region which includes atoms from three of the four subunits [12].
• Complete nucleotide sequence of the fumarase gene fumA, of Escherichia coli [13].
• Class I contains fumarases A and B, which have amino acid sequences that are 90% identical to each other, but have almost no similarity to the sequence of porcine fumarase [14].
• The iron-containing FumA fumarase is the more abundant enzyme under most conditions of aerobic cell growth except when iron is limiting; FumC, which lacks iron, appears to be a backup enzyme that is synthesized optimally only when iron is low or when superoxide radicals accumulate [15].
• Several other genes including the sdhA-D, sucA-D, and fumA genes, encoding key constituents of the Krebs cycle, proved to be repressed by the loss of both transcription factors [16].

Associations of ECs2318 with chemical compounds

• The isomerization reaction apparently takes place at the same active site as the fumarase reaction since both reactions show a similar sensitivity to inactivation by O2, both reactions are strongly inhibited by 2-hydroxy-3-nitropropionate, and the isomerization reaction is inhibited by fumarate and malate [10].
• In this work it is shown that purified fumarase A contains a [4Fe-4S] cluster [14].
• Fumarase A and aconitase, two enzymes with 4Fe-4S clusters that bind a linear 4-carbon dicarboxylic acid moiety in the trans conformation during their normal hydro-lyase reaction, do catalyze this isomerization [10].
• The A-site has been demonstrated by studying crystalline fumarase with the bound competitive inhibitors-citrate and 1,2,4,5-benzenetetracarboxylic acid [17].
• (The mobility of fumarase A in native polyacrylamide gel electrophoresis and the elution volume on a gel permeation column indicate that it is a homodimer.) Its visible and circular dichroism spectra are characteristic of proteins containing an Fe-S cluster [14].

Analytical, diagnostic and therapeutic context of ECs2318

• Molecular cloning, nucleotide sequence and expression of a Sulfolobus solfataricus gene encoding a class II fumarase [18].

References