title: The structure of trp pseudorepressor at 1.65A shows why indole propionate acts as a trp 'inducer'.
abstract: The trp repressor is a small dimeric regulatory protein which controls the expression of three operons in Escherichia coli. The inactive aporepressor protein must bind two molecules of L-tryptophan to form the active repressor. If desamino analogues of L-tryptophan such as indole propionate (IPA) are substituted for L-tryptophan, an inactive pseudorepressor is formed. Because the desamino analogues thus cause derepression of operons under control of the trp repressor, they appear to be 'inducers'. We have determined the crystal structure of the pseudorepressor and refined it to 1.65 A. The molecular structure was compared to that of the nearly isomorphous orthorhombic form of the repressor. Surprisingly, the indole ring of IPA is in the same position as the indole ring of L-tryptophan in the repressor, but is 'flipped over'. As a result, the carboxyl group of IPA is oriented toward the DNA-binding surface of the protein and is in a position where it sterically and electrostatically repels the phosphate backbone of both operator and non-operator DNA. This explains why IPA acts as an apparent trp inducer.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637.
authors.forename: C L
authors.initials: CL
authors.lastname: Lawson
authors.forename: P B
authors.initials: PB
authors.lastname: Sigler
mesh_terms: D001059:Apoproteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics*; D005786:Gene Expression Regulation; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D012097:Repressor Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism; D014364:Tryptophan / Q000031:analogs & derivatives*
chemical_list: D001059:Apoproteins; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012097:Repressor Proteins; D014157:Transcription Factors; D014364:Tryptophan