The medical domain

Epigenetic defects (gain or loss of DNA methylation) of the human ICR1 11p15 domain result in two opposite foetal growth disorders (BWS and SRS) depending on which parental allele is affected. A few deletions within ICR1 have been reported in familial BWS cases with ICR1 gain of methylation, however the mechanism(s) of the DNA methylation defects at ICR1 remains largely unknown in most BWS and SRS patients.

83p runthenight07 01-03-2023 9 3   Download

The transcription factor serum response factor (SRF) regulates expression of growth factor-dependent genes and muscle-specific genes in vertebrates. Homologous factors regulate differentiation of some ectodermic tissues in invertebrates. To explore the molecular basis of these different physiological functions, the functionality of human, Drosophila melanogaster and Artemia franciscana SRFs in mammalian cells has been compared in this article. D. melanogaster and, to a lesser extend, A.

9p system191 01-06-2013 32 5   Download

The human immunodeficiency virus type 1, HIV-1, genome encodes a highly conserved regulatory gene product, Vpr (96 amino acids), which is incorporated into virions in quantities equivalent to those of the viral Gag protein. In infected cells, Vpr is believed to function during the early stages of HIV-1 replication (such as transcription of the proviral genome and migration of preintegration nuclear complex), blocks cells in G2 phase and triggers apoptosis.

10p system191 01-06-2013 46 4   Download

We report here the full coding sequence of a novel mouse putative membrane-associated mucin containing three extracellular EGF-like motifs and a mucin-like domain consisting of at least 20 tandem repeats of 124–126 amino acids. Screening a cosmid and a BAC libraries allowed to isolate several genomic clones. Genomic and cDNA sequence comparisons showed that the gene consists of 25 exons and 24 introns covering a genomic region of  52 kb. The first intron is  16 kb in length and is followed by an unusually large exon ( 9.5 kb) encoding Ser/Thr-rich tandemly repeated sequences....

10p system191 01-06-2013 44 4   Download

The interaction of blood coagulation factor X and its Gla-containing fragments with negatively charged phospholipid membranes composed of 25 mol% phosphatidylserine (PtdSer) and 75 mol% phosphatidylcholine (PtdCho) was studied by surface plasmon resonance. The binding to 100 mol% PtdCho membranes was negligible. The calcium dependence in the membrane binding was evaluated for intact bovine factor X (factor X) and the fragment containing the Gla-domain and the N-terminal EGF (epidermal growth factor)-like domain, Gla–EGFN, from factor X....

6p system191 01-06-2013 30 4   Download

A series of thylakoid membrane proteins, including PsbX, PsbY and PsbW, are synthesized with cleavable signal peptides yet inserted using none of the known Sec/SRP/Tat/ Oxa1-type insertion machineries. Here, we show that, although superficially similar to Sec-type signal peptides, these thylakoidal signal peptides contain very different determinants.

11p system191 01-06-2013 46 4   Download

UMR 5539 (CNRS) Laboratoire de Motilite Cellulaire (Ecole Pratique des Hautes Etudes), Universite de Montpellier, France; ´ Centre de Recherches de Biochimie Macromoleculaire, Montpellier, France; 3Genes and Development Group, Department of Biomedical Sciences, University of Edinburgh, Scotland It is generally assumed that of the six domains that comprise gelsolin, domain 2 is primarily responsible for the initial contact with the actin filament that will ultimately result in the filament being severed.

11p system191 01-06-2013 38 5   Download

The siglecs (sialic acid-binding Ig-like lectins) are a distinct subset of the Ig superfamily with adhesion-molecule-like structure. We describe here a novel member of the siglec protein family that shares a similar structure including five Ig-like domains, a transmembrane domain, and a cytoplasmic tail containing two ITIM-signaling motifs. Siglec10 was identified through database mining of an asthmatic eosinophil EST library. Using the Stanford G3 radiation hybrid panel we were able to localize the genomic sequence of siglec-10 within the cluster of genes on chromosome 19q13.

14p system191 01-06-2013 43 6   Download

The Department of Biochemistry and Molecular Biology, 2CREST of Japan Science and Technology Corporation; 3The Department of Nephrology and Endocrinology, Faculty of Medicine, The University of Tokyo, Japan We have cloned cDNA for leukotriene B4 12-hydroxydehydrogenase (LTB 4 12-HD)/15-ketoprostaglandin 13-reductase (PGR) from guinea-pig liver. LTB4 12-HD catalyzes the conversion of LTB4 into 12-keto-LTB4 in the presence of NADP1, and plays an important role in inactivating LTB4.

9p system191 01-06-2013 42 4   Download

Angiotensin converting enzyme (ACE) was already discovered in insects in 1994, but its physiological role is still enigmatic. We have addressed this problem by purifying four new ACE substrates from the ovaries of the grey fleshfly, Neobellieria bullata. Their primary structures were identified as NKLKPSQWISLSD (Neb-ODAIF-11)13), NKLKPSQWI (Neb-ODAIF-11)9), SLKPSNWLTPSE (Neb-ODAIF-2) and LEQIYHL. Database analysis showed significant homology with amino acid sequence stretches as present in the N-terminal part of several fly yolk proteins....

9p research12 01-06-2013 36 3   Download

The Arabidopsis FAE1 b-ketoacyl-CoA synthase (FAE1 KCS) catalyzes the condensation of malonyl-CoA with longchain acyl-CoAs. Sequence analysis of FAE1 KCS predicted that this condensing enzyme is anchored to a membrane by two adjacent N-terminal membrane-spanning domains. In order to characterize the FAE1 KCS and analyze its mechanism, FAE1 KCS and its mutants were engineered with a His6-tag at their N-terminus, and expressed in Saccharomyces cerevisiae. The membrane-bound enzyme was then solubilized and purified to near homogeneity on a metal affinity column.

9p research12 01-06-2013 46 3   Download

The centromere–kinetochore complex is a highly specialized chromatin domain that both mediates and monitors chromosome–spindle interactions responsible for accurate partitioning of sister chromatids to daughter cells. Centromeres are distinguished from adjacent chromatin by specific patterns of histone modification and the presence of a centromere-specific histone H3 variant (e.g. CENP-A). Centromere-proximal regions usually correspond to sites of avid and persistent sister chromatid cohesion mediated by the conserved cohesin complex.

15p research12 01-06-2013 49 4   Download

Integrin a2b1 is the major receptor for collagens in human tissues, being involved in cell adhesion and the control of collagen and collagenase gene expression. The collagen binding site of a2b1 has been localized to the a2 von Willebrand Factor type A (VWFA) domain (A-domain or I-domain) and the residues responsible for the interaction with collagen have been mapped. We report a study of a2 VWFA domain in which residue E318, which lies outside the collagen binding site, is mutated to tryptophan, showing that this is a gain-of-function mutation. ...

9p research12 01-06-2013 35 5   Download

Csk-binding protein⁄phosphoprotein associated with glycosphingolipid-enriched domains is a transmembrane adaptor protein primarily involved in negative regulation of T-cell activation by recruitment of C-terminal Src kinase (Csk), a protein tyrosine kinase which represses Src kinase activity through C-terminal phosphorylation. Recruitment of Csk occurs via SH2-domain binding to PAG pTyr317, thus, the interaction is highly dependent on phosphorylation performed by the Src family kinase Fyn, which docks onto PAG using a dual-domain binding mode involving both SH3- and SH2-domains of Fyn....

12p research12 29-04-2013 40 3   Download

The cytochrome P450 family of enzymes has long been known tometabolize a wide range of compounds, including many of today’s most common drugs. A novel nuclear receptor called PXR has been established as an activator of several of the cytochrome P450 genes, including CYP3A4. This enzyme is believed to account for the metabolism of more than 50% of all prescription drugs. PXR is therefore used as a negative selector target and discriminatory filter in preclinical drug development.

9p research12 29-04-2013 44 3   Download

Chimeric calcium/calmodulin dependent protein kinase (CCaMK) is characterized by the presence of a visinin-like Ca 2+ -binding domain unlike other known calmodulin-dependent kinases. Ca 2+ -Binding to the visinin-like domain leads to autophosphorylation and changes in the affinity for calmodulin [Sathyanarayanan P.V., Cremo C.R. & Poovaiah B.W. (2000)J. Biol. Chem. 275, 30417–30422]. Here, we report that the Ca 2+ -stimulated autophosphory-lation of CCaMK results in time-dependent loss of enzyme activity. ...

7p research12 29-04-2013 31 3   Download

Biosynthesis of cholesterol represents one of the funda-mental cellular metabolic processes. SterolD14-reductase (D14-SR) is a microsomal enzyme involved in the con-version of lanosterol to cholesterol in mammals. Amino-acid sequence analysis of a 38-kDa protein puri®ed from bovine liver in our laboratory revealed 90% similarity with a human sterol reductase, SR-1, encoded by the TM7SF2gene, and with the C-terminal domain of human lamin B receptor.

8p research12 29-04-2013 38 3   Download

Membrane-bound transhydrogenases are conformationally driven proton-pumps which couple an inward proton translocation to the reversible reduction of NADP + by NADH(forward reaction). This reaction is stimulatedby an electrochemical protongradient,Dp, presumably throughan increased release of NADPH. The enzymes have three domains: domain II spans the membrane, while domain I and III are hydrophilic and contain the binding sites for NAD(H) andNADP(H), respectively.

11p research12 23-04-2013 35 3   Download

A new approach of predicting structural classes of protein domain sequences is presented in this paper. Besides the amino acid composition, the composition of several dipeptides, tripeptides, tetrapeptides, pentapeptides and hexapeptides are taken into account based on the step-wise discriminant analysis. The result of jackknife test shows that this new approach can lead to higher pre-dictive sensitivityand specificityfor reduced sequence similaritydatasets.

7p research12 23-04-2013 32 3   Download

The estrogen receptor-related receptorc (ERRc/ERR3/ NR3B3) is an orphan member of the nuclear receptor superfamily closely related to the estrogen receptors. To explore the DNA binding characteristics, the protein–DNA interaction was studied in electrophoretic mobility shift assays (EMSAs). In vitro translated ERRc binds as a homodimer to direct repeats (DR) without spacing of the nuclear receptor half-site 5¢-AGGTCA-3¢(DR-0), to exten-dedhalf-sites, and to the inverted estrogen response element....

12p research12 23-04-2013 22 3   Download