👤 C. Shobha Devi

The classical view of protein function based on rigid, well-defined structures is being redefined by the emerging concept of intrinsic disorder. Conditionally disordered proteins (CDPs) represent a subset of cellular intrinsically disordered proteins (IDPs) that transition between ordered and disordered states in response to specific stimuli, such as redox changes, post-translational modifications, ligand binding, interaction with partners, or environmental stress. This review explores the diverse landscape of conditional disorder and encompasses cryptic or dormant disordered regions, redox-sensitive motifs, metamorphic proteins, and proteins exhibiting order–disorder–new order transitions. These dynamic transitions allow CDPs to perform specialized regulatory, signalling, and stress-responsive roles, which often act as interaction hubs in complex cellular networks. Importantly, conditional disorder is not an anomaly but a conserved and functionally relevant feature across many proteomes. We highlight mechanistic insights into disorder-to-order transitions and their implications for cellular plasticity, adaptability, and disease. We also discuss how the conformational heterogeneity of CDPs complicates structure-based drug design, while offering unique therapeutic opportunities. Future directions include the integration of advanced biophysical techniques, computational modelling, and profiling to map, characterize, and target CDPs with greater precision. Overall, understanding the molecular logics of the conditional disorder will open new frontiers in structural biology and offer a deeper appreciation of protein versatility beyond static structural paradigms. Show less

DNA structure has many potential places where endogenous compounds and xenobiotics can bind. Therefore, xenobiotics bind along the sites of the nucleic acid with the aim of changing its structure, its genetic message, and, implicitly, its functions. Currently, there are several mechanisms known to be involved in DNA binding. These mechanisms are covalent and non-covalent interactions. The covalent interaction or metal base coordination is an irreversible binding and it is represented by an intra-/interstrand cross-link. The non-covalent interaction is generally a reversible binding and it is represented by intercalation between DNA base pairs, insertion, major and/or minor groove binding, and electrostatic interactions with the sugar phosphate DNA backbone. In the present review, we focus on the types of DNA–metal complex interactions (including some representative examples) and on presenting the methods currently used to study them. Show less

Two Ru(II) complexes [Ru(phen)2bppp](ClO4)2 (1) and [Ru(phen)27-Br-dppz](ClO4)2 (2) [phen=1,10 phenanthroline, 7-Br-dppz=7-fluorodipyrido[3,2-a:2',3'-c]phenazine, bppp=11-bromo-pyrido[2',3':5,6]pyrazino[2,3-f] [1,10]phenanthroline] have been synthesized and characterized by elemental analysis, ES-MS, (1)H-NMR, (13)C-NMR and IR. The in vitro cytotoxicity of the complexes examined against a panel of cancer cell lines (HeLa, Du145 and A549) by MTT method, both complexes show prominent anticancer activity against various cancer cells. Live cell imaging study and flow cytometric analysis demonstrate that both the complexes 1 and 2 could cross the cell membrane accumulating in the nucleus. Further, flow cytometry experiments showed that the cytotoxic Ru(II) complexes 1 and 2 induced apoptosis of HeLa tumor cell lines. Photo induced DNA cleavage studies have been performed and results indicate that both the complexes efficiently photo cleave pBR322 DNA. The binding properties of two complexes toward CT-DNA were investigated by various optical methods and viscosity measurements. The experimental results suggested that both Ru(II) complexes can intercalate into DNA base pairs. The complexes were docked into DNA-base pairs using the GOLD docking program. Show less