Yanofsky

The elegant genetic studies by the group of Charles Yanofsky at Stanford University, conducted before the crystal structure was known, confirm this mechanism. The side chain of Ala 77, which is in the loop region of the helix-turn-helix motif, faces the cavity where tryptophan binds. When this side chain is replaced by the bulkier side chain of Val, the mutant repressor does not require tryptophan to be able to bind specifically to the operator DNA. The presence of a bulkier valine side chain at position 77 maintains the heads in an active conformation even in the absence of bound tryptophan. The crystal structure of this mutant repressor, in the absence of tryptophan, is basically the same as that of the wild-type repressor with tryptophan. This is an excellent example of how ligand-induced conformational changes can be mimicked by amino acid substitutions in the protein. 

Yanofsky NN, Nierenberg D, Turco JH (1991) Acute short-term memory loss from trimethyltin exposure. Journal of Emergency Medicine, 9 137-139. 

Kamath AV, C Yanofsky (1992) Characterization of the tryptophanase operon in Proteus vulgaris. J Biol Chem 267 19978-19985. 

As an offshoot of studies of genes concerned with the biosynthesis of amino acids, a range of E. coli (see, e.g., Yanofsky, 1971) and Salmonella typhimurium strains (see, e.g., Ames, 1971) with relatively well-defined mutations in known genes... 

Yanofsky, C. (1971). Mutagenesis studies with Escherichia coli mutants with known amino acid and base-pair) changes. In Chemical Mutagens, Principles and Methods for Their Detection (Hollaender A., Ed.). Vol. 1, Plenum Press, New York, pp. 283-287. 

Leroux, B. Yanofsky, M.F. Winans, S.C. Ward, J.E. Ziegler, S.E Nester, E.W. Characterization of the virA locus of Agrobacterium tumefaciens a transcriptional regulator and host range determinant. EMBO J., 6, 849-856 (1987)... 

Yanofsky, C., Konan, K.V., Sarsero, J.P. (1996) Some novel transcription attenuation mechanisms used by bacteria. Biochimie... 

Attenuation. A major mechanism of feedback repression, known as attenuation, depends not upon a repressor protein but upon control of premature termination. It was first worked out in detail by Yanofsky et al. for the trp operon of E. coli and related bacteria.184 186 Accumulation of tryptophan in the cell represses the trp biosynthetic operon by the action of accumulating tryptophanyl-tRNATlP, which specifically induces termination in the trp operon. Other specific "charged" arnino-acyl-tRNA molecules induce termination at other amino acid synthesis operons. 

Among the genes concerned with biosynthetic processes, those uniquely involved in synthesis of the amino acid tryptophan are possibly the best understood. This is mostly a result of the efforts of Charles Yanofsky and his colleagues, who have used a wide variety of genetic and biochemical techniques to probe the complexities of this system. 

Yanofsky, C., Operon-specific control by transcription attenuation. Trends Genet. 3 356-360, 1987. 

Zurawski G, Brown KD, Killingly D, Yanofsky C (1978) Proc Natl Acad Sci USA 75 4271... 

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