Partial Intrinsic Disorder Governs the Dengue Capsid Protein Conformational Ensemble

Published date : 24 May 2018

The 11 kDa, positively charged dengue capsid protein (C protein) exists stably as a homodimer and co-localizes with the viral genome within mature viral particles. Its core is composed of four alpha helices encompassing a small hydrophobic patch that may interact with lipids, but approximately 20% of the protein at the N-terminus is intrinsically disordered, making it challenging to elucidate its conformational landscape.

type
Journal Paper
journal
ACS Chemical Biology 2018 Jun 15;13(6):1621-1630. doi: 10.1021/acschembio.8b00231
Impact Factor
4.592

Isolation and Identification of an Anthracimycin Analogue from Nocardiopsis kunsanensis, a Halophile from a Saltern, by Genomic Mining Strategy

Published date : 21 May 2018

Modern medicine is unthinkable without antibiotics; yet, growing issues with microbial drug resistance require intensified search for new active compounds. Natural products generated by Actinobacteria have been a rich source of candidate antibiotics, for example anthracimycin that, so far, is only known to be produced by Streptomyces species. Based on sequence similarity with the respective biosynthetic cluster, we sifted through available microbial genome data with the goal to find alternative anthracimycin-producing organisms.

type
Journal Paper
journal
Journal of Genomics, Vol. 6, 2018, Pg 63-73, doi:10.7150/jgen.24368
Impact Factor
2.402

Gene expression profile analysis of aortic vascular smooth muscle cells reveals upregulation of cadherin genes in myocardial infarction patients

Published date : 18 May 2018

Myocardial infarction (MI) induced by acute coronary arterial occlusion is usually secondary to atherosclerotic plaque rupture. Dysregulated response of vascular smooth muscle cells (VSMCs) in atherosclerotic plaques may promote plaque rupture. Cadherins (CDHs) form adherens junctions and are known stabilizers of atherosclerotic plaques. To date, the expression patterns of cadherin have not been well investigated in MI aortic VSMCs. We aimed to investigate the expression of cadherin genes in the aortic wall of patients with and without MI.

type
Journal Paper
journal
Physiological Genomics, 18 May 2018, doi: 10.1152/physiolgenomics.00042.2017
Impact Factor
2.782

Antimicrobial activity profiles of Amphiphilic Xanthone derivatives are a function of their molecular Oligomerization

Published date : 18 May 2018

Currently, membrane-targeting small antimicrobial peptidomimetics (SAP) are important in antibiotic development because bacteria appear to develop resistance to these surface-active compounds less readily. However, the molecular membrane-targeting action of SAPs has received little attention. In this study, we investigated the effect of oligomerization of amphiphilic xanthone, a model SAP, on its antimicrobial properties against both Gram-positive and Gram-negative bacteria.

type
Journal Paper
journal
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2018, doi: 10.1016/j.bbamem.2018.05.006
Impact Factor
3.498

A Thermodynamic Funnel Drives Bacterial Lipopolysaccharide Transfer in the TLR4 Pathway

Published date : 17 May 2018

The Gram-negative bacterial outer membrane contains lipopolysaccharide, which potently stimulates the mammalian innate immune response. This involves a relay of specialized complexes culminating in transfer of lipopolysaccharide from CD14 to Toll-like receptor 4 (TLR4) and its co-receptor MD-2 on the cell surface, leading to activation of downstream inflammatory responses. In this study we develop computational models to trace the TLR4 cascade in near-atomic detail.

type
Journal Paper
journal
Structure, 26, Pg 1-11, July 3, 2018, doi: 10.1016/j.str.2018.04.007
Impact Factor
4.907

Conformational landscape of the epidermal growth factor receptor kinase reveals a mutant specific allosteric pocket

Published date : 16 May 2018

Activating mutations within the epidermal growth factor receptor (EGFR) kinase domain give rise to several cancers including Non-Small Cell Lung Cancer (NSCLC). Small molecule inhibitors targeted at these mutants have proven to be clinically successful drugs. These molecules are ATP competitive and rapidly result in the emergence of resistance. Recently Jia et al.

type
Journal Paper
journal
Chemical Science, 2018, doi: 10.1039/C8SC01262H
Impact Factor
8.668

Function of a membrane-embedded domain evolutionarily multiplied in the GPI lipid anchor pathway proteins PIG-B, PIG-M, PIG-U, PIG-W, PIG-V, and PIG-Z

Published date : 15 May 2018

Distant homology relationships among proteins with many transmembrane regions (TMs) are difficult to detect as they are clouded by the TMs’ hydrophobic compositional bias and mutational divergence in connecting loops. In the case of several GPI lipid anchor biosynthesis pathway components, the hidden evolutionary signal can be revealed with dissectHMMER, a sequence similarity search tool focusing on fold-critical, high complexity sequence segments.

type
Journal Paper
journal
Cell Cycle, Vol 17, 2018, Issue 7, doi: 10.1080/15384101.2018.1456294
Impact Factor
3.304

Discovering novel SNPs that are correlated with patient outcome in a Singaporean cancer patient cohort treated with gemcitabine-based chemotherapy

Published date : 11 May 2018

Background
Single Nucleotide Polymorphisms (SNPs) can influence patient outcome such as drug response and toxicity after drug intervention. The purpose of this study is to develop a systematic pathway approach to accurately and efficiently predict novel non-synonymous SNPs (nsSNPs) that could be causative to gemcitabine-based chemotherapy treatment outcome in Singaporean non-small cell lung cancer (NSCLC) patients.

type
Journal Paper
journal
BMC Cancer (2018), 18:555, doi: 10.1186/s12885-018-4471-x
Impact Factor
3.288

Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH2

Published date : 11 May 2018

Linear antimicrobial peptides, with their rapid bactericidal mode of action, are well-suited for development as topical antibacterial drugs. We recently designed a synthetic linear 4-residue peptide, BRBR-NH2, with potent bactericidal activity against Staphylococcus aureus (MIC 6.25 μM), the main causative pathogen of human skin infections with an unknown mechanism of action.

type
Journal Paper
journal
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2018, doi: 10.1016/j.bbamem.2018.05.004
Impact Factor
3.498

Role of the serotonergic pathway in uterotonic activity of Ananas comosus (L.) Merr. – An in vitro and in vivo study

Published date : 08 May 2018

Background
Ananas comosus (L.) Merr. has been used as a traditional medicine in inducing abortion in many countries. Our previous in vitro experiments showed that the aqueous fraction (F4) of A. comosus extract stimulated the rat and human uterine contractions.

Purpose
The aim of this study was to identify the bioactive compound and further investigate the molecular mechanism of F4 induced contraction and the in vivo uterotonic effect of F4.

type
Journal Paper
journal
Phytomedicine, Vol. 48, 15 Sept 2018, Pg 32-42, doi: 10.1016/j.phymed.2018.05.004
Impact Factor
3.610