Target dependency structures

Nitrogen monoxide (NO) is a cytotoxic effector molecule produced by macrophages that results in Fe mobilization from tumour target cells which inhibits DNA synthesis and mitochondrial respiration. It is well known that NO has a high affinity for Fe, and we showed that NO-mediated Fe mobilization is markedly potentiated by glutathione (GSH) generated by the hexose monophosphate shunt [Watts, R.N. & Richardson, D.R. (2001) J. Biol. Chem. 276, 4724–4732]. We hypothesized that GSH completes the coordination shell of an NO–Fe complex that is released from the cell.

10p research12 01-06-2013 47 3   Download

Antizyme is a polyamine-induced cellular protein that binds to ornithine decarboxylase (ODC), and targets it to rapid ubiquitin-independent degradation by the 26S proteasome. However, the metabolic fate of antizyme is not clear. We have tested the stability of antizyme in mammalian cells. In contrast with previous studies demonstrating stability in vitro in a reticulocyte lysate-based degradation system, in cells antizyme is rapidly degraded and this degradation is inhibited by specific proteasome inhibitors. ...

7p research12 01-06-2013 40 3   Download

Emerin is a ubiquitously expressed inner nuclear membrane protein of unknown function. Mutations in its gene give rise to X-linked Emery–Drei-fuss muscular dystrophy (X-EDMD), a neuromuscular condition with an associated life-threatening cardiomyopathy. We have previously reported that emerin is phosphorylated in a cell cycle-dependent manner in human lymphoblastoid cell lines [Ellis et al. (1998) Aberrant intracellular targeting and cell cycle-dependent phosphorylation of emerin contribute to the EDMD phenotype.J. Cell Sci. 111, 781–792]. ...

14p research12 29-04-2013 41 4   Download

All living organisms contain redox systems involving thior-edoxins (Trx), proteins featuringanextremelyconservedand reactive active site that perform thiol-disul®de interchanges with disul®de bridges of target proteins. In photosynthetic organisms, numerous isoforms of Trx coexist, as revealedby sequencing ofArabidopsisgenome. The speci®c functions of many of them are still unknown.

11p research12 29-04-2013 34 2   Download

Correct sorting of newly synthesized peroxisomal matrix proteins is dependent on a peroxisomal targeting signal (PTS).So far two PTSs are known.PTS1 consists of a tripeptide that is located at the extremeCterminus ofmatrix proteins and is specifically recognized by the PTS1-receptor Pex5p.We studied Hansenula polymorpha Pex5p (HpPex5p) using fluorescence spectroscopy.The intensity of Trp fluorescence of purified HpPex5p increased by 25% upon shifting the pH frompH 6.0 to pH 7.2.

7p tumor12 20-04-2013 38 4   Download

Calpain 1 behaviour toward cytoskeletal targets was inves-tigated using twoa-actinin isoforms from smooth and skel-etal muscles. These two isoforms which are, respectively, sensitiveandresistant tocalpaincleavage, interactwiththe protease when usinginvitro binding assays. The stability of the complexes in EGTA [Kd(–Ca2+)¼0.5 ± 0.1lM] was improved in the presence of 1 mMcalcium ions [Kd(+Ca2+)¼0.05 ± 0.01lM]. Location of the binding structures shows that the C-terminal domain ofa-actinin and each calpain subunit, 28 and 80 kDa, participates in the interaction....

9p fptmusic 12-04-2013 44 2   Download

The glyoxalase pathway ofLeishmania infantumwas kinetically character-ized as a trypanothione-dependent system. Using time course analysis based on parameter fitting with a genetic algorithm, kinetic parameters were estimated for both enzymes, with trypanothione derived substrates. A Kmof 0.253 mmand aVof 0.21lmolÆmin )1 Æmg )1 for glyoxalase I, and a Kmof 0.098 mmand aVof 0.18lmolÆmin )1 Æmg )1 for glyoxalase II, were obtained.

11p awards 06-04-2013 46 2   Download

Cytosolic phospholipase A2 -a (cPLA2 -a) is a calcium-activated enzyme involved in agonist-induced arachidonic acid release. In endothelial cells, free arachidonic acid is predominantly converted into prostacyclin, a potent vaso-dilator and inhibitor of platelet activation. As the rate-lim-iting step in prostacyclin production is the generation of free arachidonic acid by cPLA2-a, this enzyme has become an attractive pharmacological target and the focus of many studies.

9p dell39 03-04-2013 40 4   Download

Signal transducer and activator of transcription 2 (STAT2) is best known as a critical transactivator component of the interferon-stimulated gene factor 3 (ISGF3) complex that drives the expression of many interferon (IFN)-inducible genes. However, STAT2 is also involved in DNA binding in non-ISGF3 transcriptional complexes.

13p inspiron33 26-03-2013 34 4   Download

Lpx1p (systematic name: Yor084wp) is a peroxisomal protein fromSaccha-romyces cerevisiae with a peroxisomal targeting signal type 1 (PTS1) and a lipase motif. Using mass spectrometry, we have identified Lpx1p as present in peroxisomes, and show that Lpx1p import is dependent on the PTS1 receptor Pex5p.

11p media19 05-03-2013 30 2   Download

Macroautophagy (hereafter referred to as autophagy) is a tightly regulated lysosome-dependent catabolic pathway. During this process, cytosolic con-stituents are sequestered into autophagosomes, which subsequently fuse with lysosomes to become autolysosomes, where their contents are degraded.

13p viettel02 20-02-2013 45 3   Download

The copines are a family of C2- and von Willebrand factor A-domain-con-taining proteins that have been proposed to respond to increases in intra-cellular calcium by translocating to the plasma membrane. The copines have been reported to interact with a range of cell signalling and cytoskele-tal proteins, which may therefore be targeted to the membrane following increases in cellular calcium.

16p viettel02 19-02-2013 43 2   Download