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11.
The mechanism-based inhibition of dopamine beta-hydroxylase (DBH; EC 1.14.17.1) by p-cresol (4-methylphenol) and other simple structural analogues of dopamine, which lack a basic side-chain nitrogen, is reported. p-Cresol binds DBH by a mechanism that is kinetically indistinguishable from normal dopamine substrate binding [DeWolf, W. E., Jr., & Kruse, L. I. (1985) Biochemistry 24, 3379]. Under conditions (pH 6.6) of random oxygen and phenethylamine substrate addition [Ahn, N., & Klinman, J. P. (1983) Biochemistry 22, 3096] p-cresol adds randomly, whereas at pH 4.5 or in the presence of fumarate "activator" addition of p-cresol precedes oxygen binding as is observed with phenethylamine substrate. p-Cresol is shown to be a rapid (kinact = 2.0 min-1, pH 5.0) mechanism-based inactivator of DBH. This inactivation exhibits pseudo-first-order kinetics, is irreversible, is prevented by tyramine substrate or competitive inhibitor, and is dependent upon oxygen and ascorbic acid cosubstrates. Inhibition occurs with partial covalent incorporation of p-cresol into DBH. A plot of -log kinact vs. pH shows maximal inactivation occurs at pH 5.0 with dependence upon enzymatic groups with apparent pK values of 4.51 +/- 0.06 and 5.12 +/- 0.06. p-Cresol and related alkylphenols, unlike other mechanism-based inhibitors of DBH, lack a latent electrophile. These inhibitors are postulated to covalently modify DBH by a direct insertion of an aberrant substrate-derived benzylic radical into an active site residue. 相似文献
12.
An interstitial duplication of the X chromosome in a male allows physical fine mapping of probes from the Xq13-q22 region 总被引:8,自引:2,他引:6
F. P. M. Cremers R. A. Pfeiffer T. J. R. van de Pol M. H. Hofker T. A. Kruse B. Wieringa H. H. Ropers 《Human genetics》1987,77(1):23-27
Summary An insertional translocation into the proximal long arm of the X chromosome in a boy showing muscular hypotony, growth retardation, psychomotor retardation, cryptorchidism, and Pelizaeus-Merzbacher disease (PMD) was identified as a duplication of the Xq21–q22 segment by employing DNA probes. With densitometric scanning for quantitation of hybridization signals, 15 Xq probes were assigned to the duplicated region. Analysis of the duplication allowed us to dissect the X-Y homologous region physically at Xq21 and to refine the assignments of the loci for DXYS5, DXYS12, DXYS13, DXS94, DXS95, DXS96, DXS111, and DXS211. Furthermore, we demonstrated the presence of two different DXYS13, and DXS17 alleles in genomic DNA of our patient, suggesting that the duplication resulted from a meiotic recombination event involving the two maternal X chromosomes. 相似文献
13.
beta-Ethynyltyramine has been shown to be a potent, mechanism-based inhibitor of dopamine beta-hydroxylase (DBH). This is evidenced by pseudo-first-order, time-dependent inactivation of enzyme, a dependence of inactivation on the presence of ascorbate and oxygen cosubstrates, the ability of tyramine (substrate) and 1-(3,5-difluoro-4-hydroxybenzyl)imidazole-2-thione (competitive multisubstrate inhibitor) to protect against inactivation, and a high affinity of beta-ethynyltyramine for enzyme. Inactivation of DBH by beta-ethynyltyramine is accompanied by stoichiometric, covalent modification of the enzyme. Analysis of the tryptic map following inactivation by [3H]-beta-ethynyltyramine reveals that the radiolabel is associated with a single, 25 amino acid peptide. The sequence of the modified peptide is shown to be Cys-Thr-Gln-Leu-Ala-Leu-Pro-Ala-Ser-Gly-Ile-His-Ile-Phe-Ala-Ser-Gln-Leu- His*- Thr-His-Leu-Thr-Gly-Arg, where His* corresponds to a covalently modified histidine residue. In studies using the separated enantiomers of beta-ethynyltyramine, we have found the R enantiomer to be a reversible, competitive inhibitor versus tyramine substrate with a Ki of 7.9 +/- 0.3 microM. The S enantiomer, while also being a competitive inhibitor (Ki = 33.9 +/- 1.4 microM), is hydroxylated by DBH to give the expected beta-ethynyloctopamine product and also efficiently inactivates the enzyme [kinact(app) = 0.18 +/- 0.02 min-1; KI(app) = 57 +/- 8 microM]. The partition ratio for this process is very low and has been estimated to be about 2.5. This establishes an approximate value for kcat of 0.45 min(-1) and reveals that (S)-beta-ethynyltyramine undergoes a slow turnover relative to that of tyramine (kcat approximately 50 s(-1), despite the nearly 100-fold higher affinity of the inactivator for enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
14.
Paul G. Layer Regina Alber Patrick Mansky Günter Vollmer Elmar Willbold 《Cell and tissue research》1990,259(2):187-198
Summary We report here that similar to E6-chicken retinal cells, dissociated cells from 5.5-day-old (E5.5) quail retinae reaggregate in rotary culture, multiply about tenfold and reestablish histotypical areas. These cellular aggregates include all nuclear layers either with inversed or correct laminar polarity, depending on the local origin of the cells (called rosetted and laminar in-vitro-retinae (IVR), respectively; Layer and Willbold 1989). In combined cultures, chick and quail cells are evenly mixed only during the first two days of culture. Along with the assembly of single cells into rosettes and then into discrete laminae, sectors of chick and quail cells begin to segregate. They are delineated by borders running radially through all three nuclear layers. Thus, interspecies migration of cells at this advanced stage of differentiation is strongly inhibited. Concomitant with this segregation, coherent radial columns spanning all three layers but containing cells from either species only, can be traced histologically. We conclude that a weak segregation of chick and quail retinal cells takes place already at the single cell level, but that the permanent segregation of entire tissue parts must be due to clonal cellular proliferation within the IVR in conjunction with some developmental-structural mechanism retaining clonal progenies within a columnar order.Abbreviations
ECM
extracellular matrix
-
E5.5
days of embryonic age
-
GCL
ganglion cell layer
-
GC's
ganglion cells
-
i.c.
in culture
-
INL
inner nuclear layer
- rosetted in-vitro-retina
retinal cell organoid aggregated from single cells of the central retina
-
IPL
inner plexiform layer
-
MRE
marginal retinal epithelium
-
ONL
outer nuclear layer
-
OPL
outer plexiform layer
-
OS
ora serrate
-
PR
photoreceptor cell
- laminated in-vitro-retina
fully laminated retinal cellorganoid resembling an E15-retina aggregated from cells of the eye periphery including RPE
-
RPE
retinal pigment epithelium 相似文献
15.
Regeneration of transgenic plants of Prunus armeniaca containing the coat protein gene of Plum Pox Virus 总被引:1,自引:0,他引:1
Margit Laimer da Câmara Machado Artur da Câmara Machado Veronika Hanzer Hans Weiss Ferdinand Regner Herta Steinkellner Diethard Mattanovich Regina Plail Elisabeth Knapp Birgit Kalthoff Hermann Katinger 《Plant cell reports》1992,11(1):25-29
Summary A system was developed which allows the transfer of foreign genes into apricot cultivars. We report the transformation and regeneration of Prunus armeniaca plants with Agrobacterium tumefaciens strain LBA 4404 containing various binary plasmids, pBinGUSint, carrying the marker gene ß-glucuronidase (GUS) and pBinPPVm, carrying the coat protein gene of Plum Pox Virus (PPV). The marker gene GUS was used for optical evaluation of the efficiency of the transformation system. The coat protein gene of PPV was used to introduce coat protein mediated resistance against one of the most important pathogens of stone fruit trees in Europe and the whole Mediterranean area. This is the first report of the successful integration of a viral coat protein gene into a fruit tree species, opening a new perspective on the control of the disease.Abbreviations GUS
ß-glucuronidase
- PPV
Plum Pox Virus
- BA
6-benzylaminopurine
- NPTII
neomycin phosphotransferase II
- CP
coat protein
- CaMV
Cauliflower Mosaic Virus
- P35S 35S
promoter
- MS
Murashige and Skoog
- PCR
polymerase chain reaction
- P/C/I
phenol/chloroform/isoamylalcohol
- RNase
ribonuclease
- dNTP
deoxyribonucleosidetriphosphate
- DMSO
dimethyl sulfoxide 相似文献
16.
17.
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20.
Linkage relationships and gene order around the locus for X-linked retinoschisis. 总被引:10,自引:3,他引:7 下载免费PDF全文
T Alitalo H Forsius J Krn R R Frants A W Eriksson S Wood T A Kruse A de la Chapelle 《American journal of human genetics》1988,43(4):476-483
X-linked recessive retinoschisis (RS) is a hereditary disorder with variable clinical features. The main symptoms are poor sight; radial, cystic macula degeneration; and peripheral superficial retinal detachment. The disease is quite common in Finland, where at least 300 hemizygous males have been diagnosed. We used nine polymorphic DNA markers to study the localization of RS on the short arm of the X chromosome in 31 families comprising 88 affected persons. Two-point linkage results confirmed close linkage of the RS gene to the marker loci DXS43, DXS16, DXS207, and DXS41 and also revealed close linkage to the marker loci DXS197 and DXS9. Only one recombination was observed between DXS43 and RS in 59 informative meioses, giving a maximum lod score of 13.87 at the recombination fraction .02. No recombinations were observed between the RS locus and DXS9 and DXS197 (lods between 3 and 4), but at neither locus was the number of informative meioses sufficient to provide reliable estimates of recombination fractions. The most likely gene order on the basis of multilocus analysis was Xpter-DXS85-(DXS207,DXS43)-RS-DXS41-DXS 164-Xcen. Because multilocus linkage analysis indicated that the most probable location of RS is proximal to DXS207 and DXS43 and distal to DXS41, these three flanking markers are the closest and most informative markers currently available for carrier detection. 相似文献