A computational subtractive genome analysis for the characterization of novel drug targets in Klebsiella pneumonia strain PittNDM01

2020 ◽  
Vol 146 ◽  
pp. 104245
Author(s):  
Humaira Rafiq ◽  
Kalim Ullah ◽  
Bashir Ahmad ◽  
Ashfaq Ur Rehman ◽  
Mian Khaqan Shah ◽  
...  
Keyword(s):  
Genome Analysis ◽  
Drug Targets ◽  
Klebsiella Pneumonia ◽  
Novel Drug ◽  
Novel Drug Targets

Apicoplast Metabolism: Parasite’s Achilles’ Heel

2019 ◽  
Vol 18 (22) ◽  
pp. 1987-1997 ◽  
Author(s):  
Kavita Kadian ◽  
Yash Gupta ◽  
Harsh Vardhan Singh ◽  
Prakasha Kempaiah ◽  
Manmeet Rawat
Keyword(s):  
Drug Targets ◽  
Mep Pathway ◽  
Antibacterial Drug ◽  
Methylerythritol Phosphate ◽  
Combination Drugs ◽  
Current Therapies ◽  
Novel Drug ◽  
Rapid Emergence ◽  
Novel Drug Targets

Malaria continues to impinge heavily on mankind, with five continents still under its clasp. Widespread and rapid emergence of drug resistance in the Plasmodium parasite to current therapies accentuate the quest for novel drug targets and antimalarial compounds. Plasmodium parasites, maintain a non-photosynthetic relict organelle known as Apicoplast. Among the four major pathways of Apicoplast, biosynthesis of isoprenoids via Methylerythritol phosphate (MEP) pathway is the only indispensable function of Apicoplast that occurs during different stages of the malaria parasite. Moreover, the human host lacks MEP pathway. MEP pathway is a validated repertoire of novel antimalarial and antibacterial drug targets. Fosmidomycin, an efficacious antimalarial compound against IspC enzyme of MEP pathway is already in clinical trials as a combination drugs. Exploitation of other enzymes of MEP pathway would provide a much-needed impetus to the antimalarial drug discovery programs for the elimination of malaria. We outline the cardinal features of the MEP pathway enzymes and progress made towards the characterization of new inhibitors.

Molecular and catalytic properties of an arginine kinase from the nematode Ascaris suum

2011 ◽  
Vol 86 (3) ◽  
pp. 276-286 ◽  
Author(s):  
M. Nagataki ◽  
K. Uda ◽  
B.R. Jarilla ◽  
S. Tokuhiro ◽  
S. Wickramasinghe ◽  
...  
Keyword(s):  
Drug Targets ◽  
Ascaris Suum ◽  
Arginine Kinase ◽  
Catalytic Efficiency ◽  
Significant Activity ◽  
High Amino Acid ◽  
Gene Structures ◽  
Novel Drug ◽  
Novel Drug Targets

AbstractWe amplified the cDNA coding for arginine kinase (AK) from the parasitic nematode Ascaris suum, cloned it in pMAL plasmid and expressed the enzyme as a fusion protein with the maltose-binding protein. The whole cDNA was 1260 bp, encoding 400 amino acids, and the recombinant protein had a molecular mass of 45,341 Da. Ascaris suum recombinant AK showed significant activity and strong affinity ( K _{m}^{Arg} = 0.126\hairsp mM) for the substrate l-arginine. It also exhibited high catalytic efficiency ( k _{cat}/ K _{m}^{Arg} = 352) comparable with AKs from other organisms. Sequence analysis revealed high amino acid sequence identity between A. suum AK and other nematode AKs, all of which cluster in a phylogenetic tree. However, comparison of gene structures showed that A. suum AK gene intron/exon organization is quite distinct from that of other nematode AKs. Phosphagen kinases (PKs) from certain parasites have been shown to be potential novel drug targets or tools for detection of infection. The characterization of A. suum AK will be useful in the development of strategies for control not only of A. suum but also of related species infecting humans.

scholarly journals Application of Proteomics in Biomarker Discovery: a Primer for the Clinician

2010 ◽  
pp. 471-497
Author(s):  
V Tambor ◽  
A Fučíková ◽  
J Lenčo ◽  
M Kacerovský ◽  
V Řeháček ◽  
...  
Keyword(s):  
Drug Targets ◽  
Biomarker Discovery ◽  
Protein Quality ◽  
Clinical Proteomics ◽  
Plasma Biomarker ◽  
Diagnostic Biomarkers ◽  
Current State ◽  
Novel Drug ◽  
Novel Drug Targets

Ever since proteomics was proven to be capable of characterizing a large number of differences in both protein quality and quantity, it has been applied in various areas of biomedicine, ranging from the deciphering molecular pathogenesis of diseases to the characterization of novel drug targets and the discovery of potential diagnostic biomarkers. Indeed, the biomarker discovery in human plasma is clearly one of the areas with enormous potential. However, without proper planning and implementation of specific techniques, the efforts and expectations may very easily be hampered. Numerous earlier projects aimed at clinical proteomics, characterized by exaggerated enthusiasm, often underestimated some principal obstacles of plasma biomarker discovery. Consequently, ambiguous and insignificant results soon led to a more critical view in this field. In this article, we critically review the current state of proteomic approaches for biomarker discovery and validation, in order to provide basic information and guidelines for both clinicians and researchers. These need to be closely considered prior to initiation of a project aimed at plasma biomarker discovery. We also present a short overview of recent applications of clinical proteomics in biomarker discovery.

scholarly journals Characterization of the erythrocyte GTPase Rac1 in relation to Plasmodium falciparum invasion

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Silvio Paone ◽  
Sarah D’Alessandro ◽  
Silvia Parapini ◽  
Francesco Celani ◽  
Valentina Tirelli ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Host Cell ◽  
Drug Targets ◽  
Parasitophorous Vacuole ◽  
Erythrocyte Invasion ◽  
Inhibitory Compounds ◽  
Novel Drug ◽  
Novel Drug Targets

AbstractMalaria is still a devastating disease with 228 million cases globally and 405,000 lethal outcomes in 2018, mainly in children under five years of age. The threat of emerging malaria strains resistant to currently available drugs has made the search for novel drug targets compelling. The process by which Plasmodium falciparum parasites invade the host cell has been widely studied, but only a few erythrocyte proteins involved in this process have been identified so far. The erythrocyte protein Rac1 is a GTPase that plays an important role in host cell invasion by many intracellular pathogens. Here we show that Rac1 is recruited in proximity to the site of parasite entry during P. falciparum invasion process and that subsequently localizes to the parasitophorous vacuole membrane. We also suggest that this GTPase may be involved in erythrocyte invasion by P. falciparum, by testing the effect of specific Rac1 inhibitory compounds. Finally, we suggest a secondary role of the erythrocyte GTPase also in parasite intracellular development. We here characterize a new erythrocyte protein potentially involved in P. falciparum invasion of the host cell and propose the human GTPase Rac1 as a novel and promising antimalarial drug target.

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