Proteolytic enzymes

About: Proteolytic enzymes is a research topic. Over the lifetime, 23096 publications have been published within this topic receiving 835544 citations.

Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease

Abstract: We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of ‘genomic convergence’ to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1β. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.

ESTHER, the database of the α/β-hydrolase fold superfamily of proteins: tools to explore diversity of functions

Abstract: The ESTHER database, which is freely available via a web server (http://bioweb.ensam.inra.fr/esther) and is widely used, is dedicated to proteins with an α/β-hydrolase fold, and it currently contains >30 000 manually curated proteins. Herein, we report those substantial changes towards improvement that we have made to improve ESTHER during the past 8 years since our 2004 update. In particular, we generated 87 new families and increased the coverage of the UniProt Knowledgebase (UniProtKB). We also renewed the ESTHER website and added new visualization tools, such as the Overall Table and the Family Tree. We also address two topics of particular interest to the ESTHER users. First, we explain how the different enzyme classifications (bacterial lipases, peptidases, carboxylesterases) used by different communities of users are combined in ESTHER. Second, we discuss how variations of core architecture or in predicted active site residues result in a more precise clustering of families, and whether this strategy provides trustable hints to identify enzyme-like proteins with no catalytic activity.

Topography of membrane concanavalin A sites modified by proteolysis.

Abstract: The topographic distribution of membrane Con A sites becomes more clustered after treatment with proteolytic enzymes. The clustered sites appear to be involved in the formation of intercellular Con A cross-bridges between agglutinated cells.

Mathematical modelling of cancer invasion of tissue: dynamic heterogeneity

Abstract: Solid tumours grow through two distinct phases: the avascular and the vascular phase. During the avascular growth phase, the size of the solid tumour is restricted largely by a diffusion-limited nutrient supply and the solid tumour remains localised and grows to a maximum of a few millimetres in diameter. However, during the vascular growth stage the process of cancer invasion of peritumoral tissue can and does take place. A crucial component of tissue invasion is the over-expression by the cancer cells of proteolytic enzyme activity, such as the urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs). uPA itself initiates the activation of an enzymatic cascade that primarily involves the activation of plasminogen and subsequently its matrix degrading protein plasmin. Degradation of the matrix then enables the cancer cells to migrate through the tissue and subsequently to spread to secondary sites in the body. In this paper we consider a relatively simple mathematical model of cancer cell invasion of tissue (extracellular matrix) which focuses on the role of a generic matrix degrading enzyme such as uPA. The model consists of a system of reaction-diffusion-taxis partial differential equations describing the interactions between cancer cells, the matrix degrading enzyme and the host tissue. The results obtained from numerical computations carried out on the model equations produce dynamic, heterogeneous spatio-temporal solutions and demonstrate the ability of a rather simple model to produce complicated dynamics, all of which are associated with tumour heterogeneity and cancer cell progression and invasion.