排序方式: 共有48条查询结果,搜索用时 93 毫秒
41.
Xi Yuan Jeyaraman Srividhya Thomas De Luca Ju-hyong E. Lee Joseph R. Pomerening 《Molecular biology of the cell》2014,25(4):441-456
Cdh1, a coactivator of the anaphase-promoting complex (APC), is a potential tumor suppressor. Cdh1 ablation promotes precocious S-phase entry, but it was unclear how this affects DNA replication dynamics while contributing to genomic instability and tumorigenesis. We find that Cdh1 depletion causes early S-phase onset in conjunction with increase in Rb/E2F1-mediated cyclin E1 expression, but reduced levels of cyclin E1 protein promote this transition. We hypothesize that this is due to a weakened cyclin-dependent kinase inhibitor (CKI)–cyclin-dependent kinase 2 positive-feedback loop, normally generated by APC-Cdh1–mediated proteolysis of Skp2. Indeed, Cdh1 depletion increases Skp2 abundance while diminishing levels of the CKI p27. This lowers the level of cyclin E1 needed for S-phase entry and delays cyclin E1 proteolysis during S-phase progression while corresponding to slowed replication fork movement and reduced frequency of termination events. In summary, using both experimental and computational approaches, we show that APC-Cdh1 establishes a stimulus–response relationship that promotes S phase by ensuring that proper levels of p27 accumulate during G1 phase, and defects in its activation accelerate the timing of S-phase onset while prolonging its progression. 相似文献
42.
Hong-Hsiang Guan King-Siang Goh Fabian Davamani Po-Long Wu Yen-Wei Huang Jeyaraman Jeyakanthan Wen-guey Wu Chun-Jung Chen 《Journal of structural biology》2010,169(3):294-303
The structures of snake venom metalloproteases (SVMPs) are proposed to be useful models to understand the structural and functional relationship of ADAM (a disintegrin and metalloprotease) which are membrane-anchored proteins involved in multiple human diseases. We have purified, sequenced and determined the structures of two new P-III SVMPs – atragin and kaouthiagin-like (K-like) from Naja atra. Atragin exhibits a known C-shaped topology, whereas K-like adopts an I-shaped conformation because of the distinct disulfide pattern in the disintegrin-like (D) domain. K-like exhibits an enzymatic specificity toward pro-TNFα with less inhibition of cell migration, but atragin shows the opposite effect. The specificity of the enzymatic activity is indicated to be dominated mainly by the local structures of SVMP in the metalloprotease (M) domain, whereas the hyper-variable region (HVR) in the cysteine-rich (C) domain is involved in a cell-migration activity. We demonstrate also a pH-dependent enzymatic activity of atragin that we correlate with the structural dynamics of a Zn2+-binding motif and the Met-turn based on the structures determined with a pH-jump method. The structural variations between the C- and I-shapes highlight the disulfide bond patterns in the D domain of the ADAM/adamalysin/reprolysins family proteins. 相似文献
43.
Madhan Jeyaraman Sathish Muthu Shilpa Sharma Charan Ganta Rajni Ranjan Saurabh Kumar Jha 《World journal of stem cells》2021,13(11):1733-1746
Adipose tissue is a compact and well-organized tissue containing a heterogeneous cellular population of progenitor cells, including mesenchymal stromal cells. Due to its availability and accessibility, adipose tissue is considered a “stem cell depot.” Adipose tissue products possess anti-inflammatory, anti-fibrotic, anti-apoptotic, and immunomodulatory effects. Nanofat, being a compact bundle of stem cells with regenerative and tissue remodeling potential, has potential in translational and regenerative medicine. Considering the wide range of applicability of its reconstructive and regenerative potential, the applications of nanofat can be used in various disciplines. Nanofat behaves on the line of adipose tissue-derived mesenchymal stromal cells. At the site of injury, these stromal cells initiate a site-specific reparative response comprised of remodeling of the extracellular matrix, enhanced and sustained angiogenesis, and immune system modulation. These properties of stromal cells provide a platform for the usage of regenerative medicine principles in curbing various diseases. Details about nanofat, including various preparation methods, characterization, delivery methods, evidence on practical applications, and ethical concerns are included in this review. However, appropriate guidelines and preparation protocols for its optimal use in a wide range of clinical applications have yet to be standardized. 相似文献
44.
A modified Goldbeter–Koshland (GK) type model is proposed to study the open signaling cascade with forward activation. Three
different regimes related to the ultrasensitivity are clearly defined. When the cascade is sufficiently long, the steady states
in the downstream cycles exhibit a limiting behavior. Meanwhile, a temporal switch-like behavior is revealed in the pre-ultrasensitivity
regime without any feedback circuitry. A detailed analysis of this phenomenon is provided. 相似文献
45.
Porkodi Jeyaraman Arunadevi Alagarraj 《Journal of biomolecular structure & dynamics》2020,38(2):488-499
AbstractA series of transition metal complexes have been synthesized from biologically active curcumin and isoniazid Schiff base. They are characterized by various spectral techniques like UV–Vis, Fourier transform infrared (FT-IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and mass spectroscopies. Moreover, elemental analysis, magnetic susceptibility and molar conductivity measurements are also carried out. All these data evidence that the metal complexes acquire square planar except zinc(II) which adopts a tetrahedral geometry, and they are non-electrolytic in nature. Groove mode of binding between the calf thymus DNA (CT DNA) and metal complexes is confirmed by electronic absorption titration, viscosity and cyclic voltammetry studies. In addition to that, all the metal complexes are able to cleave pUC 19 DNA. Optimized geometry and ground-state electronic structure calculations of all the synthesized compounds are established out by density functional theory (DFT) using B3LYP method which theoretically reveals that copper(II) complex explores higher stability and higher biological accessibility. This is experimentally corroborated by antimicrobial studies. In silico Absorption, Distribution, Metabolism, Excretion (ADME) studies reveal the biological potential of all synthesized complexes, and also biological activity of the ligand is predicted by PASS online biological activity prediction software. Molecular docking studies are also carried out to confirm the groove mode of binding and receptor–complex interactions. 相似文献
46.
Ramar Vanajothi Vedagiri Hemamalini Jeyaraman Jeyakanthan 《Journal of biomolecular structure & dynamics》2020,38(9):2800-2808
Abbreviations ADME absorption, distribution, metabolism, and excretion MMGB/SA molecular mechanics generalized born surface area IFD induced fit docking RTK receptor tyrosine kinase NSCLC non-small-cell lung cancer ATP adenosine triphosphate OPLS optimized potential for liquid stimulation RMSD root mean square deviation HTVS high-throughput virtual screening SP standard precision XP extra precision OPLS-AA optimized potential for liquid stimulation-all atom MD molecular simulation MME molecular mechanics energies SGB surface generalized born POPC membrane 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine membrane PDB Protein Data Bank DDR1 discoidin domain receptor 1 DDR2 discoidin domain receptor 2 DDRs discoidin domain receptors ECM extracellular matrix TIP4P transferable intermolecular potential 4 point NPT constant particle number, pressure and temperature RMSF root mean square fluctuation Communicated by Ramaswamy H. Sarma 相似文献
47.
Muthukumarasamy Uthayakumar Bowdadu Benazir Sanjeev Patra Marthandan Kirti Vaishnavi Manickam Gurusaran Kanagarajan Sureka Jeyaraman Jeyakanthan Kanagaraj Sekar 《基因组蛋白质组与生物信息学报(英文版)》2012,10(4):217-225
Analysis of protein sequences from Mycobacterium tuberculosis H37Rv(Mtb H37Rv) was performed to identify homopeptide repeatcontaining proteins(HRCPs).Functional annotation of the HRCPs showed that they are preferentially involved in cellular metabolism.Furthermore,these homopeptide repeats might play some specific roles in protein-protein interaction.Repeat length differences among Bacteria,Archaea and Eukaryotes were calculated in order to identify the conservation of the repeats in these divergent kingdoms.From the results,it was evident that these repeats have a higher degree of conservation in Bacteria and Archaea than in Eukaryotes.In addition,there seems to be a direct correlation between the repeat length difference and the degree of divergence between the species.Our study supports the hypothesis that the presence of homopeptide repeats influences the rate of evolution of the protein sequences in which they are embedded.Thus,homopeptide repeat may have structural,functional and evolutionary implications on proteins. 相似文献
48.
Ansuman Biswas Subbarao Jasti Jeyaraman Jeyakanthan 《Journal of biomolecular structure & dynamics》2017,35(10):2136-2154
Thymidylate kinase (TMK) is a key enzyme for the synthesis of DNA, making it an important target for the development of anticancer, antibacterial, and antiparasitic drugs. TMK homologs exhibit significant variations in sequence, residue conformation, substrate specificity, and oligomerization mode. However, the influence of sequence evolution and conformational dynamics on its quaternary structure and function has not been studied before. Based on extensive sequence and structure analyses, our study detected several non-conserved residues which are linked by co-evolution and are implicated in the observed variations in flexibility, oligomeric assembly, and substrate specificity among the homologs. These lead to differences in the pattern of interactions at the active site in TMKs of different specificity. The method was further tested on TMK from Sulfolobus tokodaii (StTMK) which has substantial differences in sequence and structure compared to other TMKs. Our analyses pointed to a more flexible dTMP-binding site in StTMK compared to the other homologs. Binding assays proved that the protein can accommodate both purine and pyrimidine nucleotides at the dTMP binding site with comparable affinity. Additionally, the residues responsible for the narrow specificity of Brugia malayi TMK, whose three-dimensional structure is unavailable, were detected. Our study provides a residue-level understanding of the differences observed among TMK homologs in previous experiments. It also illustrates the correlation among sequence evolution, conformational dynamics, oligomerization mode, and substrate recognition in TMKs and detects co-evolving residues that affect binding, which should be taken into account while designing novel inhibitors. 相似文献