Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gene regulation by steroid hormones is mediated through an interaction of the hormone receptors with DNA regulatory sequences called hormone regulatory or responsive elements (HRE). An analysis of the HRE's in the DNA of mouse mammary tumour provirus, human metallothionein IIA gene, chicken lysozyme gene, chicken and Xenopus vitellogenin genes, growth hormones genes, Moloney murine sarcoma provirus, rabbit uteroglobin gene, rat tyrosine aminotransferase gene, rat tryptophan oxygenase gene and rat acidic glycoprotein gene, yields the following consensus for positively modulated glucocorticoid responsive elements (GRE): 5'-GGTACAnnnTGTTCT-3'. This element can also mediate induction by progesterone and probably by androgens, but not by estrogens. Detailed analysis of the DNA protection pattern suggests that a dimer of the hormone receptor interacts with this palindromic 15-mer. In genes that are negatively regulated by glucocorticoids an imperfect copy of the GRE is found, and repression is probably due to competition between hormone receptor and other transcription factors or enhancer binding proteins for binding to overlapping DNA sequences. The receptors without bound hormone are able to interact specifically with DNA in vitro, but binding of hormone is needed for transcriptional activation in vivo. This could be due, at least in part, to changes in the rate parameters of the receptor-DNA interaction induced by binding of the hormone to the receptor. The possible role of precise chromatin organization in glucocorticoid induction is discussed on the basis of the nucleosome phasing found in the LTR region of mouse mammary tumour virus.
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PMID:DNA regulatory elements for steroid hormones. 266 21

Three "P-box" amino acids within the DNA recognition alpha-helix of members of the steroid hormone and thyroid hormone families of nuclear receptors are known to determine the identity of two of the six base pairs within the half-sites of cognate DNA elements. We introduced P-box substitutions derived from different members of the thyroid hormone/estrogen receptor (T3R/ER) family into the beta-isoform of human thyroid hormone receptor (hT3R beta) and tested the DNA binding and transactivation activities of these mutants using thyroid hormone response elements (TREs) with half-sites composed of different sequences and arranged in different orientations. Different P-box sequences derived from the T3R/ER family resulted in distinct DNA binding specificities determined by the fourth base pair of the half-site. Thyroid hormone receptor mutants containing EGA, EAA, EGS substitutions for the wild type EGG P-box bound with wild type affinity to consensus AGGTCA half-sites, regardless of orientation. TREs composed of AGGACA half-sites bound hT3R beta s with an EGG or EAA P-box sequence, but not those with EGA or EGS P-box sequence. A reversal of this specificity was observed on a direct repeat TRE with AGGGCA half-sites. Additionally, an ESG P-box substitution in hT3R beta prevented the receptor from binding to a direct repeat as a homodimer, but this mutant could bind as a heterodimer with retinoid X receptor or to the everted repeat TRE from the chicken lysozyme promoter.
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PMID:The effects of P-box substitutions in thyroid hormone receptor on DNA binding specificity. 798 45

Thyroid hormone receptor (T3R)-accessory protein heterodimers preferentially bind to thyroid hormone response elements (TREs), which contain hexamer domains arranged as a direct repeat separated by a 4-basepair gap (DR + 4). T3R homodimers, however, preferentially bind to elements that consist of an inverted palindrome. We now report on unique T3R binding patterns and functional characteristics of two such elements that mediate T3 regulation. We performed mutational analysis of the chicken lysozyme silencer F2 (LysF2) TRE and demonstrated that the two functional binding domains are arranged as an inverted palindrome separated by 6 basepairs. Both the LysF2 TRE and the similarly arranged myelin basic protein TRE bind T3R dimers at very low T3R concentrations. Despite the high relative affinity for T3R dimer binding, the T3 induction conferred by these elements is low compared to that of previously characterized TREs with a DR + 4 arrangement. The laminin-B1 gene element, previously shown to bind retinoic acid receptor, contains at least four hexameric binding domains. All of the domains can bind T3R simultaneously and are involved in conferring T3 induction, but bind with a different pattern than that reported for retinoic acid receptor. T3R homodimer binding to a series of mutant laminin-B1 elements and T3 induction were significantly correlated (r = 0.82; P < 0.05). T3R homodimer binding to LysF2 element mutants was not correlated with T3 induction (r = 0.32; P > 0.05); however, T3R-nuclear protein heterodimer binding was significantly correlated (r = 0.67; P < 0.05). T3R-nuclear protein heterodimers, but not homodimers, bound consistently to mutations of the LysF2 element that altered the gap between hexamers. The overall discordance between strong T3R binding to these elements and weak T3 induction indicates that the unusual hexamer arrangement places the T3R complex in an unfavorable configuration for maximal T3-dependent transactivation. The differential T3 sensitivity of generalized resistance to thyroid hormone-associated T3R mutants to the LysF2 element compared with the DR + 4 arrangement suggests that these unique features may have physiological significance.
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PMID:Thyroid hormone receptor binds with unique properties to response elements that contain hexamer domains in an inverted palindrome arrangement. 813 57

Group 1B human pancreatic secretory phospholipase A(2) (hp-sPLA(2)), a digestive enzyme synthesized by pancreatic acinar cells and present in pancreatic juice, do not have antibacterial activity towards Escherichia coli. Our earlier results suggest that the N-terminal first ten amino acid residues of hp-sPLA(2) constitute major portion of the membrane binding domain of full-length enzyme and is responsible for the precise orientation of enzyme on the membrane surface by inserting into the lipid bilayers (Pande et al. (2006) Biochemistry, 45,12436-12447). In this study we report the antibacterial properties of a peptide (AVWQFRKMIK-CONH(2); N10 peptide), which corresponds to the N-terminal first ten amino acid residues of hp-sPLA(2), against E. coli. Full-length hp-sPLA(2), which contains this peptide sequence as N-terminal alpha-helix, did not showed detectable antibacterial activity. Presence of physiological concentration of salt or preincubation of N10 peptide with soluble anionic polymer inhibits the antibacterial activity indicating the importance of electrostatic interaction in binding of peptide to bacterial membrane. Addition of peptide resulted in destabilization of outer as well as inner cytoplasmic membrane of E. coli suggesting bacterial membranes to be the main target of action. N10 peptide exhibits strong synergism with lysozyme and potentiates the antibacterial activity of lysozyme. The peptide was inactive against human erythrocyte. Our result shows for the first time that a peptide fragment of hp-sPLA(2) possesses antibacterial activity towards E. coli and at subinhibitory concentration and can potentiate the antibacterial activity of membrane active enzyme. These observations suggest that N10 peptide may play an important role in the antimicrobial activity of pancreatic juice.
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PMID:Peptide derived from the lipid binding domain of Group IB human pancreatic phospholipase A(2) possesses antibacterial activity. 1961 4