Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ramakrishnan, T. (Yale University, New Haven, Conn.), and Edward A. Adelberg. Regulatory mechanisms in the biosynthesis of isoleucine and valine. I. Genetic derepression of enzyme formation. J. Bacteriol. 87:566-573. 1964.-A total of 60 mutants of Escherichia coli K-12 resistant to 10(-2)m valine were isolated from the valine-sensitive F' strain AB1206. Conjugation experiments showed that in five of these mutants the valine-resistance locus is closely linked to the structural genes governing isoleucine-valine biosynthesis. In these five valine-resistant mutants, three enzymes of the isoleucine-valine pathway were found to be coordinately derepressed: l-threonine deaminase, dihydroxy acid dehydrase, and transaminase B. Two other enzymes of this pathway, the condensing enzyme and the reductoisomerase, were unaffected. The mutation from valine-sensitivity to valine-resistance appears to have altered an operator locus, because the derepressed state is dominant over the repressed state in diploids heterozygous for the valine-resistance locus. The valine-resistant mutants excrete isoleucine into the medium. The significance of these findings with respect to the valine-sensitivity of E. coli K-12 and the regulation of the biosynthesis of isoleucine and valine by this organism are discussed.
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PMID:REGULATORY MECHANISMS IN THE BIOSYNTHESIS OF ISOLEUCINE AND VALINE. I. GENETIC DEREPRESSION OF ENZYME FORMATION. 1412 71

Ramakrishnan, T. (Yale University, New Haven, Conn.), and Edward A. Adelberg. Regulatory mechanisms in the biosynthesis of isoleucine and valine. II. Identification of two operator genes. J. Bacteriol. 89:654-660. 1965.-A tightly clustered set of five structural genes governs the synthesis of the five enzymes of isoleucine and valine biosynthesis in Escherichia coli. Three of the genes governing transaminase B, dehydrase, and threonine deaminase, are controlled by a single operator locus, designated oprA. The structural gene governing the condensing enzyme is controlled by a second operator locus, designated oprB. Both oprA and oprB have been shown to regulate structural genes which are cis, but not trans, to their own operator. No mutations have yet been found which affect the level of reductoisomerase, but the existence of a third operator controlling the synthesis of this enzyme can be inferred. Enzyme derepression resulting from mutations in oprA confers resistance to high levels of valine. Derepression of the condensing enzyme resulting from mutations in oprB confers resistance to low levels of valine, and to alpha-aminobutyric acid. The significance of these findings with respect to the valine sensitivity of E. coli strain K-12 is discussed.
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PMID:REGULATORY MECHANISMS IN THE BIOSYNTHESIS OF ISOLEUCINE AND VALINE. II. IDENTIFICATION OF TWO OPERATOR GENES. 1427 40

Ramakrishnan, T. (Yale University, New Haven, Conn.), and Edward A. Adelberg. Regulatory mechanisms in the biosynthesis of isoleucine and valine. III. Map order of the structural genes and operator genes. J. Bacteriol. 89:661-664. 1965.-A new method has been employed to determine the map order of the structural genes and operator genes governing the enzymes of the isoleucine-valine biosynthetic pathway. This method relies on the observation that phage transduction of markers carried on an F-genote leads to the establishment in the recipient of F-genotes of various lengths. Using this method, we have established that the order of loci is the following: F/ilvE ilvD ilvA oprA/ilvC/ilvB oprB. The operator locus, oprA, regulates the activity of structural genes ilvE (transaminase B), ilvD (dehydrase), and ilvA (threonine deaminase). The operator locus, oprB, regulates the activity of ilvB (condensing enzyme). An operator for ilvC (reductoisomerase) can be inferred to exist, but has not yet been detected genetically. The loci ilvB and oprB have been shown to be at the extreme right end of the sequence, but their positions relative to each other remain to be established.
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PMID:REGULATORY MECHANISMS IN THE BIOSYNTHESIS OF ISOLEUCINE AND VALINE. 3. MAP ORDER OF THE STRUCTURAL GENES AND OPERATOR GENES. 1427 41