Počet záznamů: 1

Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors

SYSNO ASEP	0446340
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors
Tvůrce(i)	Fajtová, Pavla (UOCHB-X)_{RID, ORCID} Štefanic, S. (CH) Hradilek, Martin (UOCHB-X)_ORCID Dvořák, Jan (UMG-J)_RID Vondrášek, Jiří (UOCHB-X)_{RID, ORCID} Jílková, Adéla (UOCHB-X)_{RID, ORCID} Ulrychová, Lenka (UOCHB-X)_{ORCID, RID} McKerrow, J. H. (US) Caffrey, C. R. (US) Mareš, Michael (UOCHB-X)_{RID, ORCID} Horn, Martin (UOCHB-X)_{RID, ORCID}
Celkový počet autorů	11
Zdroj.dok.	PLoS Neglected Tropical Diseases. - : Public Library of Science - ISSN 1935-2735 Roč. 9, č. 6 (2015), e0003827/1-e0003827/24
Poč.str.	24 s.
Jazyk dok.	eng - angličtina
Země vyd.	US - Spojené státy americké
Klíč. slova	Schistosoma mansoni ; schistosomiasis ; prolyl oligopeptidase ; blood fluke
Vědní obor RIV	CE - Biochemie
Vědní obor RIV – spolupráce	Ústav molekulární genetiky - Genetika a molekulární biologie
CEP	GAP302/11/1481 GA ČR - Grantová agentura ČR
	LO1302 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
Institucionální podpora	UOCHB-X - RVO:61388963 ; UMG-J - RVO:68378050
UT WOS	000357398100031
EID SCOPUS	84934784341
DOI	10.1371/journal.pntd.0003827
Anotace	Blood flukes of the genus Schistosoma cause schistosomiasis, a parasitic disease that infects over 240 million people worldwide, and for which there is a need to identify new targets for chemotherapeutic interventions. Our research is focused on Schistosoma mansoni prolyl oligopeptidase (SmPOP) from the serine peptidase family S9, which has not been investigated in detail in trematodes. We demonstrate that SmPOP is expressed in adult worms and schistosomula in an enzymatically active form. By immunofluorescence microscopy, SmPOP is localized in the tegument and parenchyma of both developmental stages. Recombinant SmPOP was produced in Escherichia coli and its active site specificity investigated using synthetic substrate and inhibitor libraries, and by homology modeling. SmPOP is a true oligopeptidase that hydrolyzes peptide (but not protein) substrates with a strict specificity for Pro at P1. The inhibition profile is analogous to those for mammalian POPs. Both the recombinant enzyme and live worms cleave host vasoregulatory, proline-containing hormones such as angiotensin I and bradykinin. Finally, we designed nanomolar inhibitors of SmPOP that induce deleterious phenotypes in cultured schistosomes. We provide the first localization and functional analysis of SmPOP together with chemical tools for measuring its activity. We briefly discuss the notion that SmPOP, operating at the host-parasite interface to cleave host bioactive peptides, may contribute to the survival of the parasite. If substantiated, SmPOP could be a new target for the development of anti-schistosomal drugs.
Pracoviště	Ústav organické chemie a biochemie
Kontakt	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434
Rok sběru	2016
Elektronická adresa	http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003827

Počet záznamů: 1