Abstract:
:The thyroglobulin type-1 (Tg-1) domain is a protein module that occurs in a variety of secreted and membrane proteins and is recognised as a potent inhibitor of cysteine peptidases. We present here some properties of the Tg-1 domain of human testican, a modularly organised proteoglycan secreted mainly by brain cells, the exact in vivo function of which is not yet clear. The domain was prepared as a recombinant protein in a Pichia pastoris expression system and its activity was demonstrated by specific and selective inhibition of cathepsin L (K(i) =0.14 nM). Interaction at high enzyme and inhibitor concentrations resulted in degradation of the domain by cathepsin L, which was not observed under conditions used for the determination of kinetic parameters. No inhibitory activity could be detected for cathepsin K, but it exhibited a very similar degradation pattern. Homology modelling provided a good explanation for the different behaviour observed with the two enzymes. Firstly, the steric fit between the interfaces of testican domain and cathepsin L is stabilised by numerous favourable forces, while no such interactions are evident in the complex with cathepsin K, and repulsive interactions even prevent access of the domain to the active site of papain. Secondly, the prolonged first loop of the domain occupies a position near the catalytic cysteine residue in a more substrate-like manner, enabling cleavage of the Gly22-Ala23 bond.
journal_name
Biol Chemjournal_title
Biological chemistryauthors
Meh P,Pavsic M,Turk V,Baici A,Lenarcic Bdoi
10.1515/BC.2005.010keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
75-83issue
1eissn
1431-6730issn
1437-4315journal_volume
386pub_type
杂志文章abstract::Dipeptidyl peptidase-IV has been demonstrated to play a role in cancer biology by many authors. Since then, additional proteins possessing similar enzymatic activity have been described and their role in cancerogenesis has been hypothesized. To assess the complexity of these 'Dipeptidyl peptidase-IV activity and/or st...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2004.067
更新日期:2004-06-01 00:00:00
abstract::The cloning of a Ca2+(0)-sensing receptor (CaR) from parathyroid and kidney, coupled with the identification of inherited disorders in Ca2+(0)-sensing resulting from inactivating or activating mutations of this CaR, has provided substantial insights into how Ca2+(0) is regulated at a systemic level. The CaR plays a ce...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1997-08-01 00:00:00
abstract::Glutaminyl cyclases (QC) catalyze the intramolecular cyclization of N-terminal glutamine residues of peptides and proteins. For a comparison of the substrate specificity of human and papaya QC enzymes, a novel continuous assay was established by adapting an existing discontinuous method. Specificity constants (kcat/Km...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2003.175
更新日期:2003-12-01 00:00:00
abstract::In pancreatic acinar cells stimulation of different intracellular pathways leads to different patterns of Ca2+ signaling. Bombesin induces activation of both phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) and phospholipase D (PLD). The latter leads to generation of diacylglycerol (DAG) in ...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.1999.111
更新日期:1999-07-01 00:00:00
abstract::Synthetic biologists aim at engineering controllable biological parts such as DNA, RNA and proteins in order to steer biological activities using external inputs. Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-t...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/hsz-2018-0309
更新日期:2019-03-26 00:00:00
abstract::Functional ribonuclease A was presented on the surface of the filamentous phage M13 by fusion to the minor coat protein. RNase activity of the fusion protein was shown by a zymogram assay. In addition, we established a modified method for preparing RNase-displaying phages without contaminating host RNases. ...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2000.024
更新日期:2000-02-01 00:00:00
abstract::A controlled interaction of materials with their surrounding biological environment is of great interest in many fields. Multifunctional coatings aim to provide simultaneous modulation of several biological signals. They can consist of various combinations of bioactive, and bioinert components as well as of reporter m...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/hsz-2016-0204
更新日期:2017-01-01 00:00:00
abstract::As a crucial protein, the herpes simplex virus 1 (HSV-1) UL2 protein has been shown to take part in various stages of viral infection, nonetheless, its exact subcellular localization and transport molecular determinants are not well known thus far. In the present study, by using live cells fluorescent microscopy assay...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2016-0268
更新日期:2017-04-01 00:00:00
abstract::We recently reported that human melanoma cells, but not benign melanocytes, aberrantly express kallikrein-related peptidase 7 (KLK7). Here, we show a KLK7 overexpression-mediated decrease of cell adhesion to extracellular matrix binding proteins, associated with downregulation of α5/β1/αv/β3 integrin expression. We al...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2017-0339
更新日期:2018-09-25 00:00:00
abstract::Molecular chaperones of the heat shock protein 70 (Hsp70) family play a crucial role in the presentation of exogenous antigenic peptides by antigen-presenting cells (APCs). In a combined biochemical and immunological approach, we characterize the biochemical interaction of tumor-associated peptides with human Hsp70 an...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2009.038
更新日期:2009-04-01 00:00:00
abstract::FK506-binding proteins (FKBPs) belong to a distinct class of immunophilins that interact with immunosuppressants. They use their peptidyl-prolyl isomerase (PPIase) activity to catalyze the cis-trans conversion of prolyl bonds in proteins during protein-folding events. FKBPs also act as a unique group of chaperones. Th...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2017-0251
更新日期:2018-04-25 00:00:00
abstract::Bone morphogenetic proteins (BMP) are dimeric factors initiating several distinct signaling cascades by binding to two types of transmembrane serine/threonine kinase receptors (BRI and BRII), and are thus regulating several steps in embryonal development and adult tissue homeostasis. BMP-2 contains two symmetrical pai...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2001.149
更新日期:2001-08-01 00:00:00
abstract::Myocardial zinc dyshomeostasis is associated with caspase-3 activation, ErbB2 degradation and apoptosis during hypoxia/reoxygenation. Zinc pyrithione replenishes intracellular zinc, suppresses caspase-3, augments ErbB2 levels and improves cell survival. We hypothesize that zinc is capable of modulating redox and endop...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2020-0167
更新日期:2020-10-25 00:00:00
abstract::Gaucher disease (GD) is a lysosomal storage disorder, caused by an impaired function of β-glucocerebrosidase, which results in accumulation of glucocerebroside in cells, and altered membrane ordering. Using electron paramagnetic resonance spin labeling, a statistically significant difference in the order parameter bet...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2017-0241
更新日期:2018-04-25 00:00:00
abstract::The enzymatic properties of glycosylphosphatidylinositol-specific phospholipase D (EC 3.1.4.50) were characterized using a 6,000-fold purified enzyme. This was obtained in 100 microg amounts from human serum with a recovery of 35%. Pure alkaline phosphatase containing one anchor moiety per molecule was used as substra...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2000.062
更新日期:2000-05-01 00:00:00
abstract::Calpain is a calcium-activated non lysosomal neutral thiol protease (EC 3.4.22.17) present in a wide variety of eukaryotic cells. Calpain is usually present as an inactive form and is activated by calcium ions and phospholipids. The ability of calpain to alter, by limited proteolysis, the activity or function of numer...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2002.079
更新日期:2002-05-01 00:00:00
abstract::Interleukin-13 (IL-13) is a T-cell-derived pleiotropic cytokine of particular medical importance because of its critical role in the development of allergic asthma. The effects of IL-13 on its target cells are mediated through a dimeric transmembrane receptor (IL-13R), which shares the IL-4Ralpha subunit with the IL-4...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2007.036
更新日期:2007-03-01 00:00:00
abstract::Parvulins belong to the family of peptidyl-prolyl cis/trans isomerases (PPIases) assisting in protein folding and in regulating the function of a broad variety of proteins in all branches of life. The human representatives Pin1 and Par14/17 are directly involved in processes influencing cellular maintenance and cell f...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/hsz-2017-0137
更新日期:2018-01-26 00:00:00
abstract::Molecular chaperones are well known as facilitators of protein folding and assembly. However, in recent years multiple chaperone-assisted degradation pathways have also emerged, including CAP (chaperone-assisted proteasomal degradation), CASA (chaperone-assisted selective autophagy), and CMA (chaperone-mediated autoph...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2010.058
更新日期:2010-05-01 00:00:00
abstract::This is the first report describing the enhancement of xylanase activity by the neutral amino acid glycine. Xylanase activity is increased seven-fold at alkaline pH in the presence of glycine and its pH optimum is shifted from pH 7 to 8 without using any protein engineering techniques. Analysis of the steady-state kin...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2007.007
更新日期:2007-01-01 00:00:00
abstract::L-Arginine:glycine amidinotransferase (AT) catalyzes the committed step in creatine biosynthesis by formation of guanidinoacetic acid, the direct precursor of creatine. The X-ray structure of the human enzyme shows a novel fold with fivefold pseudosymmetry of beta beta alphabeta-modules. These modules enclose the acti...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1997-03-01 00:00:00
abstract::Two new fluorescent labels are presented that are optimized for excitation with He/Ne laser and red diode lasers. Application in FCS and labeling of proteins and oligomers are demonstrated. A strong rise of quantum yield and emission life time upon binding to biomolecules are characteristic features of the dyes. ...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2001.062
更新日期:2001-03-01 00:00:00
abstract::One of the control mechanisms of cathepsin B biosynthesis and trafficking operates through alternative splicing of pre-mRNA. An mRNA lacking exon 2 is more efficiently translated than that containing all exons, and may be responsible for elevated biosynthesis and enzyme routing to the extracellular space, with critica...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2006.125
更新日期:2006-08-01 00:00:00
abstract::We have previously described Kunitz-type serine proteinase inhibitors purified from Bauhinia seeds. Human plasma kallikrein shows different susceptibility to those inhibitors. In this communication, we describe the interaction of human plasma kallikrein with fluorogenic and non-fluorogenic peptides based on the Bauhin...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2001.016
更新日期:2001-01-01 00:00:00
abstract::The major enzymatic activity of the ribosome is the catalysis of peptide bond formation. The active site -- the peptidyl transferase center -- is composed of ribosomal RNA (rRNA), and interactions between rRNA and the reactants, peptidyl-tRNA and aminoacyl-tRNA, are crucial for the reaction to proceed rapidly and effi...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2007.077
更新日期:2007-07-01 00:00:00
abstract::During the last decade, an increasing number of new enzymes containing glycyl radicals in their active sites have been identified and biochemically characterised. These include benzylsuccinate synthase (Bss), 4-hydroxyphenylacetate decarboxylase (Hpd) and the coenzyme B12-independent glycerol dehydratase (Gdh). These ...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2005.114
更新日期:2005-10-01 00:00:00
abstract::The ligand-activated aryl hydrocarbon receptor (AHR) is known to modulate many genes in a highly cell-specific manner, either directly or indirectly via secondary effects. In contrast, little is known about the effects of AHR deficiency on gene expression balance. We compared the transcriptome of CD4 T cells from AHR-...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2006.151
更新日期:2006-09-01 00:00:00
abstract::Nanoparticles (NPs) are recognized as an attractive vehicles for cancer treatment due to their targeted drug release. Gastric cancer is an important killer disease, and its therapy methods still need improvement. The NPs were prepared using a precipitation method, and were evaluated using transmission electron microsc...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2017-0208
更新日期:2018-02-23 00:00:00
abstract::Human adenocarcinomas overexpress a hypoglycosylated, tumor-associated form of the mucin-like glycoprotein MUC1 containing abnormal mono- and disaccharide antigens, such as Tn, sialyl-Tn, and TF, as well as stretches of unglycosylated protein backbone in the variable number of tandem repeats (VNTR) region. Both peptid...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2009.070
更新日期:2009-07-01 00:00:00
abstract::Fibroblast growth factor (FGF) receptor substrate 2 (FRS2) is a membrane-anchored docking protein that has been shown to play an important role in linking FGF, nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF) receptors with the Ras/mitogen-activated protein (MAP) kinase signaling cascade. He...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2003.134
更新日期:2003-08-01 00:00:00