Disease relevance of c0460

• It ensures very tight control of the derepression of cell death by the combination of the bacteriophage T7 RNA polymerase-lysozyme system and an inducible synthesis of antisense RNA and the Escherichia coli LacI repressor [1].
• The lactose repressor protein (LacI), the prototype for genetic regulatory proteins, controls expression of lactose metabolic genes by binding to its cognate operator sequences in E. coli DNA [2].
• The catabolite control protein (CcpA) from Bacillus megaterium is a member of the bacterial repressor protein family GalR/LacI [3].

High impact information on c0460

• After inactivation of M.Hha I and LacI, Hae II was used to completely cleave the chromosomes specifically at the inserted lacOs [4].
• The SsrA-mediated tagging and proteolysis of LacI appears to play a role in cellular adaptation to lactose availability by supporting a rapid induction of lac operon expression [5].
• SsrA-mediated tagging and proteolysis of LacI and its role in the regulation of lac operon [5].
• Purified MLAc is folded, fully functional, and binds the inducer isopropyl beta-d-thiogalactoside with the same affinity as wild-type LacI [6].
• This result compares well with a mathematical model of the binding of the regulatory proteins cAMP receptor protein (CRP) and LacI to the lac regulatory region [7].

Chemical compound and disease context of c0460

• The mutational specificity of the monofunctional alkylating agent N-propyl-N'-nitro-N-nitrosoguanidine (PNNG) has been determined through the DNA sequence characterization of 109 LacI- mutations of Escherichia coli [8].
• LacI mutations induced by doxorubicin in a wild-type, uvr(A)BC repair-proficient E. coli strain were analyzed by DNA sequencing [9].

Biological context of c0460

• In addition to providing insight into protein structure-function correlations, LacI has been utilized in a wide variety of applications both in prokaryotic gene expression and in eukaryotic gene regulation and studies of mutagenesis [2].
• Transformation with a high copy-number plasmid containing the lac operator, lac O, effectively induces kan expression by titrating LacI from the operator [10].
• When either NLS was placed at the 3' end behind a random nine base pair linker, the activity of the LacI protein depended on the sequence of the linker, and in 9 of 10 linkers tested, activity of the protein was adversely affected [11].
• At a salt concentration of 0.40 M, the Osym plasmid binding data are consistent with a model with two independent and identical binding sites for operator per LacI tetramer, in which the binding to a site on the tetramer is only slightly more favorable than the reference binding interaction [12].
• The importance of the structural determination of this domain is underscored by the high degree of sequence homology displayed within the effector binding sites among a sub-class of helix-turn-helix proteins, of which LacI and GalR are members [13].

Anatomical context of c0460

• The majority of the clonal cell lines created by establishment of the lacI-EBV vector show spontaneous LacI- frequencies of less than 10(-5) and are suitable for studies of induced mutation [14].

Associations of c0460 with chemical compounds

• In addition to defining the role of Lys55 in PurR minor groove binding, these studies provide structural insight into the minor groove binding specificities of other LacI/GalR family members that have either alanine (e.g. LacI, GalR, CcpA) or a basic residue (e.g. RafR, ScrR, RbtR) at the comparable position [15].
• In the presence of a XylS effector, such as m-methylbenzoate, the LacI protein is synthesized, preventing the expression of the killing function [16].

Other interactions of c0460

• When the NLS's were fused to the lacI gene at the 5' end, the protein produced exhibited tighter repression of beta-galactosidase expression than the unmodified LacI protein [11].

Analytical, diagnostic and therapeutic context of c0460

• Intact chromosomes from the resulting strains were prepared in agarose microbeads and methylated with Hha I (5'-GCGC) methyltransferase (M.Hha I) in the presence of lac repressor (LacI) [4].
• By using multiple excitation wavelengths and by carefully examining the behavior of the zero-ET peak during titration with LacI, we show that the LacI-9C14 loop exists exclusively in a single closed form exhibiting essentially 100% ET [17].

References