Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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The nucleotide sequences of blaLCR-1 and blaOXA-5 beta-lactamase genes have been determined. Polypeptide products of 260 and 267 amino acids with estimated molecular masses of 27 120 Da and 27,387 Da were obtained for the mature form of LCR-1 and OXA-5 proteins. A progressive alignment was used to evaluate the extent of identity between LCR-1 and OXA-5 with 29 other beta-lactamase amino acid sequences. The data showed that both belong to class D. We identified amino acids conserved in 24 positions for class A beta-lactamases and in 28 positions for five class D enzymes. The structural similarities between class A and class D beta-lactamases are more extensive than indicated by earlier biochemical studies with overall 16% identity between both classes. From the alignment, dendograms were constructed with a distance-matrix and parsimony methods which defined three major groups of proteins subdivided into clusters giving insight on beta-lactamase phylogeny and evolution.
Mol Microbiol 1992 Jun
PMID:Phylogeny of LCR-1 and OXA-5 with class A and class D beta-lactamases. 149 94

We have constructed a number of vectors which include transcriptional unit of human tPA cDNA and 100% BPV-1 DNA or 100% Lx DNA (mutant BPV variant with tandem duplication of LCR-E6-E7 region). Additional HSV-1 Tk-promoter was inserted in the flanks of viral DNAa in a set of constructions. A number of recombinant cell lines have been established by means of transformation using the constructed vectors. The increased focus formation activity and the improved vector properties were demonstrated for vector construction which included Lx DNA with additional Tk promoter for activation of early viral transcription. The possibilities of BPV-based vectors design are discussed.
Mol Biol (Mosk)
PMID:[Recombinant murine cell lines transformed by various vectors based on bovine papillomavirus type 1 and expressing human tissue plasminogen activator]. 166 73

Recent studies have demonstrated that transcriptional activation of the human adult beta-globin transgene in mice by coinsertion of the beta-globin cluster locus control region (beta-LCR) results in loss of its adult restricted pattern of expression. Normal developmental control is reestablished by coinsertion of the fetal gamma-globin transgene in cis to the adult beta-globin gene. To test the generality of this interdependence of two globin genes for their proper developmental control, we generated transgenic mice in which the human adult alpha-globin genes are transcriptionally activated by the beta-LCR either alone or in cis to their corresponding embryonic zeta-globin gene. In both cases, the human globin transgenes were expressed at the appropriate developmental period. In contrast to the beta-globin gene, developmental control of the human adult alpha-globin transgenes appears to be autonomous and maintained even when activated by an adjacent locus control region.
Mol Cell Biol 1991 Jul
PMID:Human alpha-globin genes demonstrate autonomous developmental regulation in transgenic mice. 171 Jul 71

Hexamethylene bisacetamide (HMBA) is a potent inducer of differentiation of murine erythroleukemia cells (MELC). Commitment, the irreversible initiation of the program of terminal-cell differentiation, is first detected in HMBA-sensitive DS19-SC9 MELC in culture after 10 to 12 h of exposure to HMBA. Vincristine (VC)-resistant MELC derived from the DS19-SC9 MELC line display increased sensitivity to HMBA and become committed with little or no latent period. In the present study, we showed that the MELC line R1, which is resistant to HMBA-mediated differentiation, became sensitive to inducer if selected for a low level of VC resistance (less than 10 ng of VC per ml). Four independently derived VC-resistant cell lines from HMBA-resistant R1 cells, designated R1[VCR]a to R1[VCR]d, acquired sensitivity to HMBA and the accelerated kinetics of commitment that are characteristic of VC-resistant MELC derived from the parental DS19-SC9 cells. The calcium channel blocker verapamil suppresses the VC resistance of R1[VCR] cells but does not alter the accelerated response to HMBA. In R1[VCR] cells there was no detectable increase in the level of the 140-kilodalton P-glycoprotein. Transient inhibition of protein synthesis during the latent period delays inducer-mediated commitment of VC-sensitive DS19-SC9 MELC but does not alter the accelerated commitment kinetics of R1[VCR]a cells. Previously, we have reported evidence that protein kinase C beta (PKC beta) plays a role in HMBA-induced MELC differentiation and that compared with DS19-SC9 cells, R1 cells have a relatively low level and R1[VCR]a cells have a high level of PKC beta. These findings suggest that (i) acquisition of VC resistance overcomes the block acquired by R1 cells to HMBA-mediated differentiation; (ii) the accelerated kinetics of HMBA-induced commitment of VC-resistant MELC is not dependent on the verapamil-sensitive transport channel that is responsible, at least in part, for resistance to VC; (iii) in VC-resistant MELC, there is constitutive expression or accumulation of a protein required for HMBA-induced differentiation; and (iv) an elevated level of PKC beta activity may play a role in the altered response of R1[VCR] and other VC-resistant MELC to HMBA.
Mol Cell Biol 1990 Jul
PMID:Conversion of differentiation inducer resistance to differentiation inducer sensitivity in erythroleukemia cells. 197 44

Sliding-window averaging of amino acid properties is a standard method for predicting protein secondary structure. For example, transmembrane segments are predicted to occur near the peaks in a hydropathy plot of a membrane protein. Such a scheme (linear convolutional recognizer, LCR) assigns a number (weight) to each type of monomer, and then convolutes some window function with the sequence of weights. The window has commonly been rectangular, and the weights derived from singlet amino acid frequencies in proteins of known secondary structure or from physical properties of amino acids. The accuracy of the windows and weights have remained unknown. We use linear optimization theory to develop a general method for approximating the optimal window and weights for a LCR. The method assumes that one knows the sequences of one or more chains and the locations of their "features", regions having the secondary structure of interest. We present formulae for quantifying the accuracy of predictors. We show why the optimal LCR is more accurate than methods based on the differences between singlet monomer frequencies inside and outside features. The advantage of an optimal LCR is that its weights inherently include correlations between nearby monomer positions. The optimal predictor is not perfect though. We argue that its inaccuracy is an intrinsic limitation of linear predictors based on monomer weights. As a practical example, we study predictors for transbilayer segments of membrane proteins. We estimate the optimal weights and windows for the two bacterial photosynthetic reaction centers whose three-dimensional structures are known. The resultant LCR, which is more accurate than previous ones, is still inexact. We apply it to bacteriorhodopsin and halorhodopsin. Several non-linear generalizations are examined as possible improvements to the LCR method: non-linear combinations of linear predictors and windowed Fourier transforms of the weight sequences. The former do not significantly increase the accuracy, while the latter reveal a weak negative correlation between the segments and periodic variations of the weights.
J Mol Biol 1989 Nov 05
PMID:Linear optimization of predictors for secondary structure. Application to transbilayer segments of membrane proteins. 268 29

Molecular cloning of DNA fragments between 1.5 and 8 kb from BamHI, EcoRI, HindIII, SalI, or Sau3A digests permitted the isolation of structural genes coding for TEM-1, ROB-1, OXA-1, OXA-3, OXA-4, OXA-5, PSE-1, PSE-2, PSE-3, PSE-4, CARB-3, CARB-4, AER-1, and LCR-1 beta-lactamases. Ampicillin-resistant clones were selected and it was confirmed that they contained the respective beta-lactamase genes by isoelectric focusing. Detailed physical maps of 14 different recombinant plasmids were constructed using 8 restriction endonucleases. Plasmid deletions and lacZ fusions were used to localize the beta-lactamase structural genes. DNA probes were constructed for the TEM-1, ROB-1, OXA-1, and PSE-1 genes. Under conditions of high stringency, hybridization was observed between the genes for TEM-1 and TEM-2 or TLE-1, OXA-1 and OXA-4, and PSE-1 and PSE-4 or CARB-3, while the ROB-1 gene probe showed no cross-hybridization. Such bla gene probes should facilitate studies of beta-lactamase molecular epidemiology.
Mol Gen Genet 1987 Feb
PMID:Molecular cloning and DNA homology of plasmid-mediated beta-lactamase genes. 303 34

Amplification and increased expression of the mdr1 gene associated with multidrug resistance in human tumors were found in multidrug-resistant sublines of human myelogenous leukemia K562 selected with vincristine (K562/VCR) or adriamycin (K562/ADM). In two revertant cell lines of K562/ADM, amplification of the mdr1 gene was maintained at the same level as in K562/ADM, but expression of the 4.5-kilobase mdr1 mRNA was greatly decreased, indicating that amplified genes may be inactivated at the level of transcription without a corresponding loss of amplified DNA.
Mol Cell Biol 1987 Dec
PMID:Decreased expression of the amplified mdr1 gene in revertants of multidrug-resistant human myelogenous leukemia K562 occurs without loss of amplified DNA. 348 35

Sliding-window averaging of amino acid properties is often used for predicting protein secondary structure. Such a scheme (linear convolutional recognizer, LCR) assigns a number (weight) to each type of monomer, and then convolutes a window function with the sequence of weights to yield a decision function. Features, regions having the property of interest, are predicted to occur where the decision function exceeds some threshold. A general method for approximating the best possible window and weights is presented. The needed data are the sequences of some chains and the locations of their features. The method is applied to transmembrane helices (TMH) of membrane proteins. Optimal weights and windows are calculated, using bacteriorhodopsin and photosynthetic reaction centers as the reference chains. The predictor is then tested on other proteins. No TMH are predicted in porin, whose transmembrane segments are beta-sheets. This shows that the predictor is specific for helical segments. Few segments are predicted for non-membrane globular proteins. The predictor thus correctly rejects their hydrophobic helices. Finally, the predictor is tested with some membrane proteins whose transmembrane topology is partially known. Among their TMH, the LCR is unable to resolve 6% which are closely spaced. Taking 17 as the minimum allowed length of a predicted TMH, 4% of the known ones are missed and 6% of the predicted ones are false. For a minimum length of 10, 0.5% are missed and 14% are false. The mean magnitude of the endpoint error is about four residues. Alternative prediction methods make more errors.
J Mol Biol 1993 Jul 05
PMID:Quadratic minimization of predictors for protein secondary structure. Application to transmembrane alpha-helices. 768 96

We have characterized a number of recombinant cell lines established with BPV1 and Lx1 (containing duplication of LCR-E6-E7 sequence) vectors on the basis of C127 cells. It had been shown that Lx1 based vectors possess the higher number of intracellular copies than analogous vectors on the basis of wtBPV, and most part of them is integrated into the host genome. Using various concentrations of heavy metal salts we have developed the optimized procedure for induction of recombinant tPA synthesis which is controlled by the mouse MT1 promoter. A 8-fold increase of rtPA concentration was reached in the course of induction. It had been shown that native and non-glucosylated forms of recombinant and human tPA are identical in their properties.
Mol Biol (Mosk)
PMID:[Recombinant murine cell lines, transformed by various vectors based on bovine type 1 papillomavirus and expressing human tissue plasminogen activator. II. Analysis of cell lines, producing recombinant tissue plasminogen activator]. 805 53

In multidrug-resistant (MDR) derivatives of the mouse lymphoid tumor P388, the emergence of MDR is associated with overexpression and transcriptional activation of the mdr3 gene, either in the absence of (P388/VCR-10) or concomitant with (P388/ADM-2) gene amplification. In both instances, Northern (RNA) blotting analyses have suggested the presence of altered mdr3 transcripts in these cells, possibly originating from novel transcription initiation sites. The mechanisms underlying mdr3 overexpression in these cells have been investigated. In P388/VCR-10 cells, Southern blotting analyses together with genomic DNA cloning and nucleotide sequencing have demonstrated the presence of an intact mouse mammary tumor virus (MMTV) within the boundaries of intron 1 of mdr3. cDNA cloning and nucleotide sequencing indicated that this integration event results in the synthesis and overexpression of a hybrid MMTV-mdr3 mRNA which initiates within the U3 region of the 5' long terminal repeat (LTR) of the provirus. Consequently, this mRNA lacks the normal exon 1 of mdr3 but contains (i) MMTV LTR-derived sequences at its 5' end, (ii) a novel mdr3 exon, mapping within the boundaries of intron 1 downstream of the MMTV integration site and generated by alternative splicing, and (iii) an otherwise intact 3' portion of mdr3 starting at exon 2. A similar type of analysis of P388/ADM-2 cells revealed that mdr3 overexpression in these cells is associated with the integration of an intracisternal A particle (IAP) within an L1Md repetitive element, immediately upstream of mdr3. The IAP insertion results in the overexpression of hybrid IAP-mdr3 mRNA transcripts that initiate within the 3' LTR of the IAP and which contain IAP LTR-derived sequences at the 5' end spliced 14 nucleotides upstream of the normal exon 1 of mdr3. Taken together, these results indicate that independent retroviral insertions were the initial mutagenic event responsible for mdr3 overexpression and survival during drug selection of these cell lines. Amplification of the rearranged and activated mdr3 gene copy occurred during further selection for high-level drug resistance in P388/ADM-2 cells.
Mol Cell Biol 1993 Dec
PMID:Activation of the mouse mdr3 gene by insertion of retroviruses in multidrug-resistant P388 tumor cells. 824 58


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