Abstract:
:Cysteine-bound hemes are key components of many enzymes and biological sensors. Protonation (deprotonation) of the Cys ligand often accompanies redox transformations of these centers. To characterize these phenomena, we have engineered a series of Thr78Cys/Lys79Gly/Met80X mutants of yeast cytochrome c (cyt c) in which Cys78 becomes one of the axial ligands to the heme. At neutral pH, the protonation state of the coordinated Cys differs for the ferric and ferrous heme species, with Cys binding as a thiolate and a thiol, respectively. Analysis of redox-dependent stability and alkaline transitions of these model proteins, as well as comparisons to Cys binding studies with the minimalist heme peptide microperoxidase-8, demonstrate that the protein scaffold and solvent interactions play important roles in stabilizing a particular Cys-heme coordination. The increased stability of ferric thiolate compared with ferrous thiol arises mainly from entropic factors. This robust cyt c model system provides access to all four forms of Cys-bound heme, including the ferric thiol. Protein motions control the rates of heme redox reactions, and these effects are amplified at low pH, where the proteins are less stable. Thermodynamic signatures and redox reactivity of the model Cys-bound hemes highlight the critical role of the protein scaffold and its dynamics in modulating redox-linked transitions between thiols and thiolates.
journal_name
Proc Natl Acad Sci U S Aauthors
Zhong F,Lisi GP,Collins DP,Dawson JH,Pletneva EVdoi
10.1073/pnas.1317173111subject
Has Abstractpub_date
2014-01-21 00:00:00pages
E306-15issue
3eissn
0027-8424issn
1091-6490pii
1317173111journal_volume
111pub_type
杂志文章abstract::microRNA-146a (miR-146a) has been previously implicated as an essential molecular brake, preventing immune overreaction and malignant transformation by attenuating NF-κB signaling, putatively via repression of the Traf6 and Irak1 genes. The exact contribution of miR-146a-mediated silencing of these genes to the contro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1706833114
更新日期:2017-08-22 00:00:00
abstract::A simple in vitro system that supports chromatin assembly was developed for Saccharomyces cerevisiae. The assembly reaction is ATP-dependent, uses soluble histones and assembly factors, and generates physiologically spaced nucleosomes. We analyze the pathway of histone recruitment into nucleosomes, using this system i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.17.9034
更新日期:1997-08-19 00:00:00
abstract::Previous reports of a relatively air-stable soluble hydrogenase from the photosynthetic anaerobe, Chromatium vinosum, have been substantiated. The properties of this enzyme, as seen in highly purified samples prepared by procedures that permit improved yields, are described. A possible role for flavin mediation is not...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.3.861
更新日期:1977-03-01 00:00:00
abstract::Deletion derivatives of the maize transposable element Activator (Ac) were constructed in vitro and inserted into a kanamycin resistance gene. These constructions were then introduced into tobacco protoplasts derived from plants previously transformed with Ac. The ability of each deletion derivative to excise was meas...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.23.9385
更新日期:1989-12-01 00:00:00
abstract::For length and area, a central fact is that the value of the length of a curve or the area of a surface, as given by the Lebesgue theory, is at least as great as that given by the classical formula, whenever the latter has meaning. This is now found not to be valid in higher dimensions. We give an example of a continu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.63.1.38
更新日期:1969-05-01 00:00:00
abstract::Many newly synthesized proteins have to become unfolded during translocation across biological membranes. We have analyzed the effects of various stabilization/destabilization mutations in the Ig-like module of the muscle protein titin upon its import from the N terminus or C terminus into mitochondria. The effects of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0504495102
更新日期:2005-12-13 00:00:00
abstract::A23187 is a carboxylic antibiotic that selectively transfers calcium, magnesium, and other divalent cations across biologic membranes. This ionophore was found to produce morphologic blast transformation, DNA synthesis, and mitosis in human lymphocytes. Several hours of ionophore-cell contact were necessary to produce...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.12.5088
更新日期:1974-12-01 00:00:00
abstract::The biosynthetic origin of the 10,000 molecular weight neurophysins, carriers of the peptide hormones oxytocin and vasopressin, has been studied by cell-free synthesis, Poly(A)-RNA was isolated from bovine hypothalamus and translated in a wheat germ system containing (35)S- or (3)H-labeled amino acids. A number of uni...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.8.3800
更新日期:1979-08-01 00:00:00
abstract::Phosphorylation of inositol phospholipids plays a key role in cellular regulation via the generation of intracellular second messengers. In addition, it represents a mechanism to regulate interactions of the lipid bilayer with proteins and protein scaffolds involved in vesicle budding, cytoskeletal organization, and s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0230488100
更新日期:2003-04-01 00:00:00
abstract::Complementary DNA (cDNA) specific for chick globin mRNA sequences fails to hybridize to total RNA extracted from chicken fibroblasts. After infection by Rous sarcoma virus, RNA complementary to globin cDNA is detectable in 100-500 copies per cell. Infection of fibroblasts with the transformation defective (td) deletio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.11.4464
更新日期:1975-11-01 00:00:00
abstract::Rivers around the world are being regulated by dams to accommodate the needs of a rapidly growing global population. These regulatory efforts usually oppose the natural tendency of rivers to flood, move sediment, and migrate. Although an economic benefit, river regulation has come at unforeseen and unevaluated cumulat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.22.11858
更新日期:2000-10-24 00:00:00
abstract::The ever-increasing industrial demand for nylon-6 (polycaprolactam) necessitates the development of environmentally benign methods of producing its precursor, epsilon-caprolactam, from cyclohexanone. It is currently manufactured in two popular double-step processes, each of which uses highly aggressive reagents, and e...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0506907102
更新日期:2005-09-27 00:00:00
abstract::The population genetic consequences of nearest-neighbor pollination in an outcrossing plant species were investigated through computer simulations. The genetic system consisted of two alleles at a single locus in a self-incompatible plant that mates by random pollen transfer from a neighboring individual. Beginning wi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.1.203
更新日期:1982-01-01 00:00:00
abstract::Before the origin of simple cellular life, the building blocks of RNA (nucleotides) had to form and polymerize in favorable environments on early Earth. At this time, meteorites and interplanetary dust particles delivered organics such as nucleobases (the characteristic molecules of nucleotides) to warm little ponds w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1710339114
更新日期:2017-10-24 00:00:00
abstract::The toxic, mutagenic, and carcinogenic effects of alkylating agents have been attributed to their ability to damage DNA. Reaction at the O6 position of guanine results in miscoding during DNA replication, has been shown to be mutagenic in both bacteriophage and bacteria, and may be responsible for malignant transforma...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.17.6292
更新日期:1986-09-01 00:00:00
abstract::Peripheral inhibitory nerves are physiological regulators of the contractile behavior of visceral smooth muscles. One of the transmitters responsible for inhibitory neurotransmission has been reputed to be a purine, possibly ATP. However, the exact identity of this substance has never been verified. Here we show that ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0705510104
更新日期:2007-10-09 00:00:00
abstract::The ability to be synchronized by light-dark cycles is a fundamental property of circadian clocks. Although there are indications that circadian clocks are extremely light-sensitive and that they can be set by the low irradiances that occur at dawn and dusk, this has not been shown on the cellular level. Here, we demo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0606870104
更新日期:2007-02-27 00:00:00
abstract::Two features make the tooth an excellent model in the study of evolutionary innovations: the relative simplicity of its structure and the fact that the major tooth-forming genes have been identified in eutherian mammals. To understand the nature of the innovation at the molecular level, it is necessary to identify the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.22.13056
更新日期:1998-10-27 00:00:00
abstract::In response to environmental changes, the connections ("arrows") in gene regulatory networks determine which genes modulate their expression, but the quantitative parameters of the network ("the numbers on the arrows") are equally important in determining the resulting phenotype. What are the objectives and constraint...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1114235109
更新日期:2012-03-27 00:00:00
abstract::The enhancer-binding factor NF-kappa B, which is found only in cells that transcribe immunoglobulin light chain genes, has been purified from nuclear extracts of Namalwa cells (human Burkitt lymphoma cells) by sequence-specific DNA affinity chromatography. The purified NF-kappa B has been identified as a 51-kDa polype...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.13.4700
更新日期:1988-07-01 00:00:00
abstract::The statistics of extrasolar planetary systems indicate that the default mode of planet formation generates planets with orbital periods shorter than 100 days and masses substantially exceeding that of the Earth. When viewed in this context, the Solar System is unusual. Here, we present simulations which show that a p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1423252112
更新日期:2015-04-07 00:00:00
abstract::The int-1 and int-2 genes were first isolated as targets for transcriptional activation by proviral insertion mutations in mammary carcinomas induced by the mouse mammary tumor virus (MMTV). Since these proto-oncogenes are not expressed at detectable levels in previously tested normal tissues from adult mice, we sough...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.20.7806
更新日期:1986-10-01 00:00:00
abstract::Previous studies have shown that the immunosuppressive and carcinogenic polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA) impairs Ca(2+)-dependent transmembrane signaling in human and murine lymphocytes. The purpose of the present studies was to analyze potential mechanisms of immunosuppression by ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.13.6105
更新日期:1993-07-01 00:00:00
abstract::Cyclic electron flow is increasingly recognized as being essential in plant growth, generating a pH gradient across thylakoid membrane (ΔpH) that contributes to ATP synthesis and triggers the protective process of nonphotochemical quenching (NPQ) under stress conditions. Here, we report experiments demonstrating the i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1110189108
更新日期:2011-08-09 00:00:00
abstract::Studies have shown that hemophilia B (Christmas disease; factor IX deficiency) results from many different mutations in the factor IX gene, of which greater than 95% are single nucleotide substitutions. This study has identified a previously unreported form of hemophilia B in a patient who was a somatic mosaic for a g...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.1.39
更新日期:1991-01-01 00:00:00
abstract::Resistance to thyroid hormone (RTH) is most often due to point mutations in the beta-isoform of the thyroid hormone (TH) receptor (TR-beta). The majority of mutations involve the ligand-binding domain, where they block TH binding and receptor function on both stimulatory and inhibitory TH response elements. In contras...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0903227106
更新日期:2009-06-09 00:00:00
abstract::One of the technical bottlenecks in producing nonhuman primate models is that current assisted reproductive techniques, such as in vitro culture and frozen conservation of multicell-stage embryos, often result in poor embryo quality and subsequently lead to low birth rates. We investigated whether pronuclear embryo tr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0805639105
更新日期:2008-09-02 00:00:00
abstract::Most studies on the ability of insect populations to transmit pathogens consider only constant temperatures and do not account for realistic daily temperature fluctuations that can impact vector-pathogen interactions. Here, we show that diurnal temperature range (DTR) affects two important parameters underlying dengue...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1101377108
更新日期:2011-05-03 00:00:00
abstract::Sex determination in mammals is governed by antagonistic interactions of two genetic pathways, imbalance in which may lead to disorders/differences of sex development (DSD) in human. Among 46,XX individuals with testicular DSD (TDSD) or ovotesticular DSD (OTDSD), testicular tissue is present in the gonad. Although the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1921676117
更新日期:2020-06-16 00:00:00
abstract::An array of photoreceptors including cryptochromes, phototropin, and phytochromes regulates various light responses in plants. Among these photoreceptors, phytochromes perceive red and far-red light by switching between two interconvertible spectral forms (Pr and Pfr). The Pfr form promotes light responses partly by d...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1109683109
更新日期:2012-01-24 00:00:00