ISRN Structural Biology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. AtTRB1–3 Mediates Structural Changes in AtPOT1b to Hold ssDNA Sun, 16 Feb 2014 09:44:26 +0000 POT from Arabidopsis thaliana is a member of shelterin complex and belongs to Telo_bind protein family. Three homologs are reported, namely, AtPOT1a, AtPOT1b, and AtPOT1c, where AtPOT1b is involved in genomic stability and chromosome end protection by providing necessary grip to G-rich region of telomeric DNA for telomerase assembly. Telomeric binding factors (TRB1–3) physically interact with POT with no known functionality. In this work attempt has been made to elucidate the reason behind the interaction by analyzing molecular docking interaction between AtPOT1b and AtTRB1–3, which yielded potential residues, which could play essential role in structural modification. 3 ns molecular simulation helped to look into structural stability and conformational dynamics portraying domain movements. AtTRB’s interaction with AtPOT1b provoked structural changes in AtPOT1b, thereby increasing the affinity for single strand DNA (ssDNA) as compared to double strand DNA (dsDNA). Although the obtained results require experimental evidence they can act as a guide in tracing the functions in other organisms. The information provided in this paper would be helpful in understanding functions of TRB1–3 with respect to genomic stability. Amit Jaiswal Copyright © 2014 Amit Jaiswal. All rights reserved. Human Tonic and Phasic Smooth Muscle Myosin Isoforms Are Unresponsive to the Loop 1 Insert Tue, 10 Dec 2013 15:50:20 +0000 Smooth muscle myosin gene products include two isoforms, SMA and SMB, differing by a 7-residue peptide in loop 1 (i7) at the myosin active site where ATP is hydrolyzed. Using chicken isoforms, previous work indicated that the i7 deletion in SMA prolongs strong actin binding by inhibiting active site ingress and egress of nucleotide when compared to i7 inserted SMB. Additionally, i7 deletion inhibits Pi release associated with the switch 2 closed→open transition in actin-activated ATPase. Switch 2 is far from loop 1 indicating i7 deletion has an allosteric effect on Pi release. Chicken SMA and SMB have unknown and robust nucleotide-sensitive tryptophan (NST) fluorescence increments, respectively. Human SMA and SMB both lack NST increments while Pi release in Ca2+ATPase is not impacted by i7 deletion. The NST reports relay helix movement following conformation change in switch 2 but in the open→closed transition. The NST is common to all known myosin isoforms except human smooth muscle. Other independent works on human SMA and SMB motility indicate no functional effect of i7 deletion. Smooth muscle myosin is a stunning example of species-specific myosin structure/function divergence underscoring the danger in extrapolating disease-linked mutant effects on myosin across species. Katalin Ajtai, Azad Mayanglambam, Yihua Wang, and Thomas P. Burghardt Copyright © 2013 Katalin Ajtai et al. All rights reserved. 2D-QSAR, Docking Studies, and In Silico ADMET Prediction of Polyphenolic Acetates as Substrates for Protein Acetyltransferase Function of Glutamine Synthetase of Mycobacterium tuberculosis Sun, 17 Feb 2013 13:41:43 +0000 A novel transacetylase (TAase) function of glutamine synthetase (GS) in bacterial species such as Mycobacterium smegmatis and Mycobacterium tuberculosis H37Rv was established by us, termed as mycobacterial TAase (MTAase). Several polyphenolic acetates (PAs) were found to be substrates for MTAase by inhibiting certain receptor proteins such as glutathione S-transferase by way of acetylation. The present work describes the descriptor-based 2D-QSAR studies developed for a series of PA synthesized by us and evaluated for MTAase and antimycobacterial activity using stepwise multiple linear regression method with the kinetic constants and the minimum inhibitory constant (MIC) as the dependent variables, to address the fact that TAase activity was leading to the antimycobacterial activity. Further, blind docking methods using AutoDock were carried out to study the interaction of potent PA with the crystal structure of M. tuberculosis GS. PAs were predicted to bind M. tuberculosis GS on the protein surface away from the known active site of GS. Subsequent focussed/refined docking of potent PA with GS showed that the -amino group of Lys4 of GS formed a cation- interaction with the benzene ring of PA. Also, ADMET-related descriptors were calculated to predict the pharmacokinetic properties for the selection of the effective and bioavailable compounds. Prija Ponnan, Shikhar Gupta, Madhu Chopra, Rashmi Tandon, Anil S. Baghel, Garima Gupta, Ashok K. Prasad, Ramesh C. Rastogi, Mridula Bose, and Hanumantharao G. Raj Copyright © 2013 Prija Ponnan et al. All rights reserved.