aspartic protease 5: structural basis of substrate binding and inhibition mechanism.

, a worldwide prevalent parasite is responsible for causing toxoplasmosis in almost all warm-blooded animals, including humans. Golgi-resident aspartic protease 5 (ASP5) plays an essential role in the maturation and export of the effector proteins those modulate the host immune system to establish a successful infection. Hence, inhibiting this enzyme can be a possible therapeutic strategy against toxoplasmosis.

Structures of plasmepsin X from Plasmodium falciparum reveal a novel inactivation mechanism of the zymogen and molecular basis for binding of inhibitors in mature enzyme.

Plasmodium falciparum plasmepsin X (PfPMX), involved in the invasion and egress of this deadliest malarial parasite, is essential for its survival and hence considered as an important drug target. We report the first crystal structure of PfPMX zymogen containing a novel fold of its prosegment. A unique twisted loop from the prosegment and arginine 244 from the mature enzyme is involved in zymogen inactivation; such mechanism, not previously reported, might be common for apicomplexan proteases similar to PfPMX.

Alphavirus capsid protease inhibitors as potential antiviral agents for Chikungunya infection.

Chikungunya virus (CHIKV) is an arthritogenic alphavirus and currently, no antiviral drug is available to combat it. Capsid protein (CP) of alphaviruses present at the N-terminus of the structural polyprotein possesses auto-proteolytic activity which is essential for initiating the structural polyprotein processing. We are reporting for the first time antiviral molecules targeting capsid proteolytic activity.

Structural characterization and in-silico analysis of Momordica charantia 7S globulin for stability and ACE inhibition.

Momordica charantia (Mc) seeds are widely used edible crop with high nutritional quality. The food and pharmaceutical industries use it as a natural anti-oxygenic agent. Herein, a ~52 kDa protein, which is a major part of seed proteome has been purified, biochemically characterized and structure has been determined.

Crystal structures of a putative periplasmic cystine-binding protein from Candidatus Liberibacter asiaticus: insights into an adapted mechanism of ligand binding.

The amino acid-binding receptors, a component of ABC transporters, have evolved to cater to different specificities and functions. Of particular interest are cystine-binding receptors, which have shown broad specificity. In the present study, a putative periplasmic cystine-binding protein from Candidatus Liberibacter asiaticus (CLasTcyA) was characterized.

Development of nsP2 protease based cell free high throughput screening assay for evaluation of inhibitors against emerging Chikungunya virus.

Chikungunya virus has emerged as one of the most important global arboviral threats over the last decade. Inspite of large scale morbidity, with long lasting polyarthralgia, so far no licensed vaccine or antiviral is available. CHIKV nsP2 protease is crucial for processing of viral nonstructural polypeptide precursor to release enzymes required for viral replication, thus making it a promising drug target.

Structure-function insights into chikungunya virus capsid protein: Small molecules targeting capsid hydrophobic pocket.

The crystal structure of chikungunya (CHIKV) virus capsid protease domain has been determined at 2.2Å. Structure reveals a chymotrypsin-like protease fold with a conserved hydrophobic pocket in CHIKV capsid protein (CP) for interaction with the cytoplasmic tail of E2 (cdE2) similar to the capsid protein of other alphaviruses.

A novel function for globulin in sequestering plant hormone: Crystal structure of Wrightia tinctoria 11S globulin in complex with auxin.

Auxin levels are tightly regulated within the plant cell, and its storage in the isolated cavity of proteins is a measure adopted by cells to maintain the availability of auxin. We report the first crystal structure of Wrightia tinctoria 11S globulin (WTG) in complex with Indole-3-acetic acid (IAA), an auxin, at 1.7 Å resolution.

Purification and Characterization of 2S Albumin from Seeds of Wrightia tinctoria Exhibiting Antibacterial and DNase Activity.

2S albumin is a low-molecular-weight seed storage protein belonging to the prolamin superfamily. In the present work a small 2S albumin (WTA) protein of ~16 kDa has been purified from the seeds of Wrightia tinctoria. The WTA is a heterodimer protein with a small subunit of ~5 kDa and a larger subunit of ~11 kDa bridged together through disulphide bonds.

Acyl chain preference and inhibitor identification of Moraxella catarrhalis LpxA: Insight through crystal structure and computational studies.

Lipopolysaccharide (LPS) is an important surface component and a potential virulence factor in the pathogenesis of Gram-negative bacteria. UDP-N-acetylglucosamine acyltransferase (LpxA) enzyme catalyzes the first reaction of LPS biosynthesis, reversible transfer of R-3-hydroxy-acyl moiety from donor R-3-hydroxy-acyl-acyl carrier protein to the 3' hydroxyl position of UDP-N-acetyl-glucosamine. LpxA enzyme's essentiality in bacterial survival and absence of any homologous protein in humans makes it a promising target for anti-bacterial drug development.

Structural, Functional and Evolutionary Aspects of Seed Globulins.

Globulins are a major class of seed storage proteins which were thought to be enzymatically inactive. These proteins belong to the most ancient cupin superfamily. They can be graded into 11S legumin type and 7S vicilin type based on their sedimentation coefficients.

Conformer and pharmacophore based identification of peptidomimetic inhibitors of chikungunya virus nsP2 protease.

Chikungunya virus nsP2 replication protein is a cysteine protease, which cleaves the nonstructural nsP1234 polyprotein into functional replication components. The cleavage and processing of nsP1234 by nsP2 protease is essential for the replication and proliferation of the virus. Thus, ChikV nsP2 protease is a promising target for antiviral drug discovery.

Structural and functional evolution of chitinase-like proteins from plants.

The plant genome contains a large number of sequences that encode catalytically inactive chitinases referred to as chitinase-like proteins (CLPs). Although CLPs share high sequence and structural homology with chitinases of glycosyl hydrolase 18 (TIM barrel domain) and 19 families, they may lack the binding/catalytic activity. Molecular genetic analysis revealed that gene duplication events followed by mutation in the existing chitinase gene have resulted in the loss of activity.