Significance of transglutaminase-catalyzed reactions in growth and development of filarial parasite, Brugia malayi

Mehta, Kapil; Rao, U. R.; Vickery, Ann C.; Birckbichler, Paul J.

doi:10.1016/s0006-291x(05)80892-7

Cited by 20 publications

(14 citation statements)

References 10 publications

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“…The unrooted tree generated by the NJ method is shown in Fig. SA (34) or even worms (35), will aid in resolving the evolutionary relationship of these different classes of proteins.…”

Section: Resultsmentioning

confidence: 99%

Organization and evolution of the human epidermal keratinocyte transglutaminase I gene.

Polakowska

Eickbush

Falciano

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Transglutaminases (TGases; protein-glutamine:amine 'glutamyltransferase, EC 2.3.2.13) are calcium-dependent crosslinking enzymes that modify proteins posttranslationally. Several distinct types of TGases have been identified, which appear to be encoded by a family of closely related genes. We isolated the gene encoding human keratinocyte-specific type I TGase (TGase I) and characterized its chromosomal organization. The TGase I gene consists of 15 exons separated by 14 introns and exhibits a restriction fragment length polymorphism. Exons appear to encode functional and/or structural domains: exon I and part of exon XV encode untranslated regions, whereas exons VII and XI contain the active site and a presumptive calcium-binding domain, respectively. Interestingly, exon VI of TGase I contains a consensus Arg-Gly-Asp tripeptide sequence whose presence suggests an intriguing extracellular function for the enzyme. We present a likely phylogenetic tree for seven known members of the TGase family based on amino acid sequence similarity. Arguments presented suggest that the active enzyme evolved first and the structural human erythrocyte membrane protein 4.2 (band 4.2) has undergone a rapid change in amino acid sequence. It follows that band 4.2 evolved from the type II TGases, whereas factor xm subunit a evolved from the type I group.

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“…The unrooted tree generated by the NJ method is shown in Fig. SA (34) or even worms (35), will aid in resolving the evolutionary relationship of these different classes of proteins.…”

Section: Resultsmentioning

confidence: 99%

Organization and evolution of the human epidermal keratinocyte transglutaminase I gene.

Polakowska

Eickbush

Falciano

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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“…The resulting bonds are covalent, stable and resistant to chemical and enzymatic degradation. The presence of transglutaminase in adult female B. malayi and its role in the in utero development of microfilariae was first reported by Mehta et al (1990). More recently, the presence of TGases in Dirofilaria immitis (Chandrashekar et al 1998), Onchocerca volvulus (Lustigman et al 1995), Acanthocheilonema viteae (Rao et al 1991), Caenorhabditis elegans (Natsuka et al 2001), and Plasmodium falciparum (Adini et al 2001) has been reported.…”

Section: Introductionmentioning

confidence: 92%

“…Transglutaminases are a family of Ca 2+ -dependent enzymes that catalyse the posttranslational modification of proteins through the exchange of primary amines for ammonia at the c-carboxy amide group of glutamine residue. Peptide bound lysine residues or polyamines serve as the primary amines to form either (c-glutamyl) lysine or (c-glutamyl) polyamine between or within the proteins (Mehta et al 1990). The resulting bonds are covalent, stable and resistant to chemical and enzymatic degradation.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of a Brugia malayi transglutaminase

Devarajan

Mishra

Thirugnanam

et al. 2004

Parasitology Research

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Prior studies have demonstrated that transglutaminase (TGase) from the human filarial parasite Brugia malayi is critical for the growth and development of the larval stages. In this report, we describe the cloning and partial characterization of a cDNA encoding the B. malayi TGase (BmTGase). Using RT-PCR and RACE-PCR, the cDNA was amplified from adult worm mRNA. BmTGase is 1,881 bp long and codes for a protein with a predicted molecular mass of 54 kDa. Amino acid sequence analysis of BmTGase revealed significant homology to the protein disulfide isomerase (PDI), particularly, to the PDI-related protein ERp60, a PDI isoform found in the lumen of endoplasmic reticulum. The activity of recombinant B. malayi TGase enzyme (rBmTG) was found to be calcium-dependent and could be inhibited by EDTA. ELISA studies showed that approximately 88% of 48 sera from healthy Indian patients living in a bancroftian filariasis endemic area were reactive with rBmTG. In contrast, only 33% of sera from patients with clinical filariasis were reactive to rBmTG. Non-endemic sera were uniformly non-reactive. Additional studies are needed to elucidate the role, if any, of B. malayi TGase in protective immunity to filariasis.

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“…In particular, the design should be based on still unidentified parasite-specific metabolic pathways or key regulatory enzymes so essential to the parasite that their interruption leads to slow or instantaneous parasite death. Recently, we described the presence of a novel protein cross-linking enzyme, transglutaminase (TGase; EC 2.3.2.13), in adult worms of B. malayi (18).…”

mentioning

confidence: 99%

“…TGase of filarial parasites (pTGase) is a 22-kDa protein whose activity was shown to be essential to the in utero growth and differentiation of microfilariae (mf) (18). Our recent studies (18a) have revealed several unique features of pTGase.…”

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confidence: 99%

Brugia malayi and Acanthocheilonema viteae: antifilarial activity of transglutaminase inhibitors in vitro

Rao

Mehta

Subrahmanyam

et al. 1991

Antimicrob Agents Chemother

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The possible involvement of transglutaminase-catalyzed reactions in survival of adult worms, microfilariae (mf), and infective larvae of the Milarial parasite Brugia malayi was studied in vitro by using the specific pseudosubstrate monodansylcadaverine (MDC) and the active-site inhibitors cystamine or iodoacetamide. These inhibitors significantly inhibited parasite mobility in a dose-dependent manner. This inhibition was associated with irreversible biochemical lesions followed by filarial death. A. structurally related, inactive analog of MDC, dimethyldansylcadaverine, did not affect the mobility or survival of the parasites. Adult worms failed to release mf when they were incubated in the presence of MDC or cystamine, and this inhibitory effect on mf release was concentration dependent. Similar embryostatic and macrofilaricidal effects of MDC were observed in Acanthocheilonema viteae adult worms. These studies suggest that transglutaminase-catalyzed reactions may play an important role in the growth, development, and survival of filarial parasites.

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Significance of transglutaminase-catalyzed reactions in growth and development of filarial parasite, Brugia malayi

Cited by 20 publications

References 10 publications

Organization and evolution of the human epidermal keratinocyte transglutaminase I gene.

Organization and evolution of the human epidermal keratinocyte transglutaminase I gene.

Molecular characterization of a Brugia malayi transglutaminase

Brugia malayi and Acanthocheilonema viteae: antifilarial activity of transglutaminase inhibitors in vitro

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