Leukocyte recruitment induced by snake venom metalloproteinases: Role of the catalytic domain.

Biochem Biophys Res Commun

Laboratory of Pathophysiology, Butantan Institute, São Paulo, 05503-900, Brazil. Electronic address:

Published: January 2020

Snake venom metalloproteinases (SVMPs) are key toxins involved in local inflammatory reactions after snakebites. This study aimed to investigate the effect of SVMP domains on the alterations in leukocyte-endothelium interactions in the microcirculation of mouse cremaster muscle. We studied three toxins: BnP1, a PI-toxin isolated from Bothrops neuwiedi venom, which only bears a catalytic domain; Jararhagin (Jar), a PIII-toxin isolated from Bothrops jararaca venom with a catalytic domain, as well as ECD-disintegrin and cysteine-rich domains; and Jar-C, which is produced from the autolysis of Jar and devoid of a catalytic domain. All these toxins induced an increase in the adhesion and migration of leukocytes. By inhibiting the catalytic activity of Jar and BnP1 with 1.10-phenanthroline (oPhe), leukocytes were no longer recruited. Circular dichroism analysis showed structural changes in oPhe-treated Jar, but these changes were not enough to prevent the binding of Jar to collagen, which occurred through the ECD-disintegrin domain. The results showed that the catalytic domain of SVMPs is the principal domain responsible for the induction of leukocyte recruitment and suggest that the other domains could also present inflammatory potential only when devoid of the catalytic domain, as with Jar-C.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2019.10.144DOI Listing

Publication Analysis

Top Keywords

catalytic domain
24
leukocyte recruitment
8
snake venom
8
venom metalloproteinases
8
domain
8
isolated bothrops
8
devoid catalytic
8
catalytic
7
jar
5
recruitment induced
4

Similar Publications

Diabetes mellitus, particularly type 2 diabetes, is a growing global health challenge characterized by chronic hyperglycemia due to insulin resistance. One therapeutic approach to managing this condition is the inhibition of α-glucosidase, an enzyme involved in carbohydrate digestion, to reduce postprandial blood glucose levels. In this study, a series of thiosemicarbazide-linked quinoline-piperazine derivatives were synthesized and evaluated for their α-glucosidase inhibitory activity, to identify new agents for type 2 diabetes management.

View Article and Find Full Text PDF

Structural determinants of oxygen resistance and Zn-mediated stability of the [FeFe]-hydrogenase from .

Proc Natl Acad Sci U S A

January 2025

Laboratory for Protein Crystallography, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.

[FeFe]-hydrogenases catalyze the reversible two-electron reduction of two protons to molecular hydrogen. Although these enzymes are among the most efficient H-converting biocatalysts in nature, their catalytic cofactor (termed H-cluster) is irreversibly destroyed upon contact with dioxygen. The [FeFe]-hydrogenase CbA5H from has a unique mechanism to protect the H-cluster from oxygen-induced degradation.

View Article and Find Full Text PDF

Microtubule-severing enzymes play essential roles in regulating diverse cellular processes, including mitosis and cytokinesis, by modulating microtubule dynamics. In the early branching protozoan parasite , microtubule-severing enzymes are involved in cytokinesis and flagellum length control during different life cycle stages, but none of them have been found to regulate mitosis in any life cycle form. Here, we report the biochemical and functional characterization of the microtubule-severing enzyme spastin in the procyclic form of .

View Article and Find Full Text PDF

The [4Fe-4S] cluster is an important cofactor of the base excision repair (BER) adenine DNA glycosylase MutY to prevent mutations associated with 8-oxoguanine (OG). Several MutYs lacking the [4Fe-4S] cofactor have been identified. Phylogenetic analysis shows that clusterless MutYs are distributed in two clades suggesting cofactor loss in two independent evolutionary events.

View Article and Find Full Text PDF

Objectives: To predict and characterize the three-dimensional (3D) structure of protein arginine methyltransferase 2 (PRMT2) using homology modeling, besides, the identification of potent inhibitors for enhanced comprehension of the biological function of this protein arginine methyltransferase (PRMT) family protein in carcinogenesis.

Materials And Methods: An method was employed to predict and characterize the three-dimensional structure. The bulk of PRMTs in the PDB shares just a structurally conserved catalytic core domain.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!