To cite this article: V. Jain, V. Prasad, P. Jadhav & P. R. Mishra (2009) Preparation and performance evaluation of saquinavir laden cationic submicron emulsions, Drug Delivery, 16:1, 37-44,
TAR RNA binding protein (TRBP) is a double-stranded RNA binding protein involved in various biological processes like cell growth, development, death, etc. The protein exists as two isoforms TRBP2 and TRBP1. TRBP2 contains additional 21 amino acids at its N-terminus, which are proposed to be involved in its membrane localization, when compared to TRBP1. The resonance assignment (19-228) of the double-stranded RNA binding domains (dsRBD 1 and 2) of TRBP2 has been reported earlier. Here, we report H,C and N resonance assignment for dsRBD1 of TRBP2 (1-105) containing the additional N-terminal residues. This assignment will provide deeper insights to understand the effect of these residues on the structure and dynamics of TRBP2 and would therefore help in further elucidating the differences in the role of these isoforms.
The toxin-antitoxin (TA) systems are small operon systems that are involved in important physiological processes in bacteria such as stress response and persister cell formation. E. coli HigBA complex belongs to the type II TA systems and consists of a protein toxin called HigB and a protein antitoxin called HigA. The toxin HigB is a ribosome-dependent endoribonuclease that cleaves the translating mRNAs at the ribosome A site. The antitoxin HigA directly binds the toxin HigB, rendering the HigBA complex catalytically inactive. The existing biochemical and structural studies had revealed that the HigBA complex forms a heterotetrameric assembly via dimerization of HigA antitoxin. Here, we report a high-resolution crystal structure of E. coli HigBA complex that revealed a well-ordered DNA binding domain in HigA antitoxin. Using SEC-MALS and ITC methods, we have determined the stoichiometry of complex formation between HigBA and a 33 bp DNA and report that HigBA complex as well as HigA homodimer bind to the palindromic DNA sequence with nano molar affinity. Using E. coli growth assays, we have probed the roles of key, putative active site residues in HigB. Spectroscopic methods (CD and NMR) and MD simulations study revealed intrinsic dynamic in antitoxin in HigBA complex, which may explain the large conformational changes in HigA homodimer in free and HigBA complexes observed previously. We also report a truncated, heterodimeric form of HigBA complex that revealed possible cleavage sites in HigBA complex, which can have implications for its cellular functions.
Rett Syndrome (RTT) is a rare monogenic progressive neurodevelopmental disorder occurring in about 1 in 10,000 live female births. RTT is usually diagnosed within the first two years of life and manifested by loss of hand skills, impaired mobility and speech, and development of stereotypical hand movements. RTT is caused by mutations in methyl CpG-binding protein 2 (MeCP2). Several years ago, we studied the most common missense mutations in MBD domain of MeCP2 both in silico and in vitro to reveal their effect on protein structure, stability and binding to DNA. A range of methods including molecular dynamics and free energy perturbation (FEP) were employed and the predictions were compared with circular dichroism and gel mobility shift assay measurements. The 13 mutations investigated at the time were T158M,
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