Identification of potent inhibitors for homoserine kinase: an integrated and kinetic study.

Leishmaniasis is caused by ∼20 species of that affects millions in endemic areas. Available therapies are not sufficient to effectively control the disease, cause severe side effects and eventually lead to drug resistance, making the discovery of novel therapeutic molecules an immediate need. Molecular target-based drug discovery, where the target is a defined molecular gene, protein or a mechanism, is a rationale driven approach for novel therapeutics.

A unique borrelial protein facilitates microbial immune evasion.

Lyme disease is a major tick-borne infection caused by a bacterial pathogen called , which is transmitted by ticks and affects hundreds of thousands of people every year. These bacterial pathogens are distinct from other genera of microbes because of their distinct features and ability to transmit a multi-system infection to a range of vertebrates, including humans. Progress in understanding the infection biology of Lyme disease, and thus advancements towards its prevention, are hindered by an incomplete understanding of the microbiology of , partly due to the occurrence of many unique borrelial proteins that are structurally unrelated to proteins of known functions yet are indispensable for pathogen survival.

Crystal structure and characterization of nucleoside diphosphate kinase from Vibrio cholerae.

Nucleoside diphosphate kinases (NDK) are ubiquitous enzymes that catalyse the transfer of the γ phosphate from nucleoside triphosphates (NTPs) to nucleoside diphosphate (NDPs), to maintain appropriate NTP levels in cells. NDKs are associated with signal transduction, cell development, proliferation, differentiation, tumor metastasis, apoptosis and motility. The critical role of NDK in bacterial virulence renders it a potential drug target.

The coiled-coil domain of glycosomal membrane-associated Leishmania donovani PEX14: cloning, overexpression, purification and preliminary crystallographic analysis.

The glycosomal membrane-associated Leishmania donovani protein PEX14, which plays a crucial role in protein import from the cytosol to the glycosomal matrix, consists of three domains: an N-terminal domain where the signalling molecule binds, a transmembrane domain and an 84-residue coiled-coil domain (CC) that is responsible for oligomerization. CCs are versatile domains that participate in a variety of functions including supramolecular assembly, cellular signalling and transport. Recombinant PEX14 CC was cloned, overexpressed, affinity-purified with in-column thrombin cleavage and further purified by size-exclusion chromatography.

PfKsgA1 functions as a transcription initiation factor and interacts with the N-terminal region of the mitochondrial RNA polymerase of Plasmodium falciparum.

The small mitochondrial genome (mtDNA) of the malaria parasite is known to transcribe its genes polycistonically, although promoter element(s) have not yet been identified. An unusually large Plasmodium falciparum candidate mitochondrial phage-like RNA polymerase (PfmtRNAP) with an extended N-terminal region is encoded by the parasite nuclear genome. Using specific antibodies against the enzyme, we established that PfmtRNAP was targeted exclusively to the mitochondrion and interacted with mtDNA.

Biochemical and biophysical characterization of gamma-glutamylcysteine synthetase.

γ-glutamylcysteine synthetase (Gcs) is a vital enzyme catalyzing the first and rate limiting step in the trypanothione biosynthesis pathway, the ATP-dependent ligation of L-Glutamate and L-Cysteine to form gamma-glutamylcysteine. The Trypanothione biosynthesis pathway is unique metabolic pathway essential for trypanosomatid survival rendering Gcs as a potential drug target. Here we report the cloning, expression, purification and characterization of Gcs.