Abstract:Motivation: A popular method for classification of protein domain movements apportions them into two main types: those with a ‘hinge’ mechanism and those with a ‘shear’ mechanism. The intuitive assignment of domain movements to these classes has limited the number of domain movements that can be classified in this way. Furthermore, whether intended or not, the term ‘shear’ is often interpreted to mean a relative translation of the domains.Results: Numbers of occurrences of four different types of residue conta… Show more
“…These results indicate that the N-terminal domain has significant conformational changes, whereas the C-terminal domain remains almost unchanged. DynDom software (55,56) was used to understand the conformational change in ppGBP structures. The analysis (Fig.…”
“…These results indicate that the N-terminal domain has significant conformational changes, whereas the C-terminal domain remains almost unchanged. DynDom software (55,56) was used to understand the conformational change in ppGBP structures. The analysis (Fig.…”
“…These distortions can either be distributed over the protein chain, or be localized at a few key residues, i. e. hinges, interconnected by predominantly rigid bodies. The identification of hinge residues is important in a variety of areas, and computational software, as for example DynDom, has been developed to determine “dynamic” domains (with dynamics referring there to differences between two static structures, and not actual flexibility), hinge axes and hinge bending residues from two protein conformers, and was successfully applied to compare structures with a resolution higher than 3 Å …”
Section: Figurementioning
confidence: 99%
“…Unassigned residues are marked by grey circles. e) 13 C chemical shift variance of the different forms observed by NMR (grey bars) and identification of residues involved in interdomain motions using the DynDom software (horizontal bars). The “dynamic” domains (in red) and the bending residues (in green) are determined by comparing pairwise the A, B, C and D chains of the X‐ray structure (PDB 1QGT) …”
Section: Figurementioning
confidence: 99%
“…Confronting the NMR data to predictions from the program DynDom designed to identify hinges from the comparison of two X‐ray structures was more successful. DynDom defines “dynamic” domains, as well as residues involved in interdomain bending (http://fizz.cmp.uea.ac.uk/dyndom/dyndomMain.do).…”
The hepatitis B virus (HBV) icosahedral nucleocapsid is assembled from 240 chemically identical core protein molecules and, structurally, comprises four groups of symmetrically nonequivalent subunits. We show here that this asymmetry is reflected in solid-state NMR spectra of the capsids, in which peak splitting is observed for a subset of residues. We compare this information to dihedral angle variations from available 3D structures and also to computational predictions of "dynamic" domains and molecular hinges. We find that although, at the given resolution, dihedral angles variations directly obtained from the X-ray structures are not precise enough to be interpreted, the chemical-shift information from NMR correlates, and interestingly goes beyond, information from bioinformatics approaches. Our study reveals the high sensitivity with which NMR can detect the residues allowing the subtle conformational adaptations needed in lattice formation. Our findings are important for understanding the formation and modulation of protein assemblies in general.
“…The movement of thumb sub-domain towards the finger sub-domain with a closure property of 72.1% was mediated by both translational (8.3 Å) and rotational motions (132.8°) with respect to the hinge residues. The parameter closure property (CP) can be used to term it as closure or twisting motion (CP > 50%: closure; CP < 50%: twisting) 26 .Figure 4Domain motion analysis showing thumb sub-domain movement of T7RNAP as it transitions from pH 5 ( a ) to pH 7.9 ( b ) as identified by Dyndom. The hinge regions are colored red and the moving domains are colored green.…”
The capability of performing an array of functions with its single subunit structure makes T7 RNA polymerase (T7RNAP) as one of the simplest yet attractive target for various investigations ranging from structure determinations to several biological tests. In this study, with the help of molecular dynamics (MD) calculations and molecular docking, we investigated the effect of varying pH conditions on conformational flexibility of T7RNAP. We also studied its effect on the interactions with a well established inhibitor (heparin), substrate GTP and T7 promoter of T7RNAP. The simulation studies were validated with the help of three dimensional reconstructions of the polymerase at different pH environments using transmission electron microscopy and single particle analysis. On comparing the simulated structures, it was observed that the structure of T7RNAP changes considerably and interactions with its binding partners also changes as the pH shifts from basic to acidic. Further, it was observed that the C-terminal end plays a vital role in the inefficiency of the polymerase at low pH. Thus, this in-silico study may provide a significant insight into the structural investigations on T7RNAP as well as in designing potent inhibitors against it in varying pH environments.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
