Abstract:
:The detailed molecular dynamics of an actual bond-breaking event in a fluctuating enzyme substrate complex is simulated. The method developed allows one to explore what type of fluctuations are involved in enzymatic reactions and to evaluate entropic contributions to enzyme catalysis. The fluctuations of the enzyme electrostatic potential are found to be a key dynamical factor in reactions that involve a large change in the polarity of the reacting bonds.
journal_name
Proc Natl Acad Sci U S Aauthors
Warshel Adoi
10.1073/pnas.81.2.444subject
Has Abstractpub_date
1984-01-01 00:00:00pages
444-8issue
2eissn
0027-8424issn
1091-6490journal_volume
81pub_type
杂志文章abstract::The envelope spike of HIV is one of the most highly N-glycosylated structures found in nature. However, despite extensive research revealing essential functional roles in infection and immune evasion, the chemical structures of the glycans on the native viral envelope glycoprotein gp120--as opposed to recombinantly ge...
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.1006498107
更新日期:2010-08-03 00:00:00
abstract::The design, realization, and test performances of an electronic junction based on single-electron phenomena that works in the air at room temperature are hereby reported. The element consists of an electrochemically etched sharp tungsten stylus over whose tip a nanometer-size crystal was synthesized. Langmuir-Blodgett...
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.93.20.10556
更新日期:1996-10-01 00:00:00
abstract::The quaternary structure of delta-aminolevulinic acid dehydratase (5-aminolaevulinate hydrolyase, EC 4.2.1.24) from bovine liver was examined by analytical ultracentrifugation, polyacrylamide gel electrophoresis, and electron microscopy. The molecular weights, determined by sedimentation-velocity and sedimentation-equ...
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.71.5.1767
更新日期:1974-05-01 00:00:00
abstract::Fatty acylation of cysteine residues provides spatial and temporal control of protein function in cells and regulates important biological pathways in eukaryotes. Although recent methods have improved the detection and proteomic analysis of cysteine fatty (S-fatty) acylated proteins, understanding how specific sites a...
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.1602244113
更新日期:2016-04-19 00:00:00
abstract::Type I interferons (IFNs) are helical cytokines that have diverse biological activities despite the fact that they appear to interact with the same receptor system. To achieve a better understanding of the structural basis for the different activities of alpha and beta IFNs, we have determined the crystal structure 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.94.22.11813
更新日期:1997-10-28 00:00:00
abstract::The formation of a fracture network is a key process for many geophysical and industrial practices from energy resource recovery to induced seismic management. We focus on the initial stage of a fracture network formation using experiments on the symmetric coalescence of two equal coplanar, fluid-driven, penny-shaped ...
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.1809233115
更新日期:2018-10-09 00:00:00
abstract::We have isolated two cDNA clones, NaPi-2 and NaPi-3, by screening rat kidney cortex and human kidney cortex cDNA libraries, respectively, for expression of sodium-dependent phosphate transport in Xenopus laevis oocytes. Substrate specificity and a detailed kinetic analysis (Na, Pi, H+ concentrations) suggested that ex...
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.90.13.5979
更新日期:1993-07-01 00:00:00
abstract::Endothelial cell growth factor (ECGF) binds specifically in vitro to membrane receptors present on the surface of several cell types, including murine and human endothelial cells and fibroblasts. Monoclonal antibodies prepared against ECGF that inhibit the mitogenic activity of the growth factor prevent receptor occup...
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.82.18.6138
更新日期:1985-09-01 00:00:00
abstract::The E6 oncoprotein of human papillomaviruses (HPVs) that are associated with cervical cancer utilizes the cellular ubiquitin-protein ligase E6-AP to target the tumor suppressor p53 for degradation. In normal cells (i.e., in the absence of E6), p53 is also a target of the ubiquitin-proteasome pathway. Under these condi...
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.031470698
更新日期:2001-01-30 00:00:00
abstract::The seventh cholera pandemic caused by Vibrio cholerae O1 El Tor (ET) has been superseded in Asia and Africa by altered ET possessing the cholera toxin (CTX) gene of classical (CL) biotype. The CL biotype of V. cholerae was isolated, along with prototypic and altered ET, during the 1991 cholera epidemic in Mexico and ...
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.1323408111
更新日期:2014-07-08 00:00:00
abstract::The product of the recA gene of E. coli has been identified by labeling proteins synthesized in UV-treated cells after infection with specialized transducing phages carrying the recA gene. Following infection of UV-treated cells by lambda precA, which carries the recA+ gene, a major protein with a molecular weight 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.73.11.3979
更新日期:1976-11-01 00:00:00
abstract::p90 ribosomal S6 kinase (RSK1) is an effector of both Ras/MEK/MAPK and PI3K/PDK1 pathways. We present evidence that RSK1 drives p27 phosphorylation at T198 to increase RhoA-p27 binding and cell motility. RSK1 activation and p27pT198 both increase in early G(1). As for many kinase-substrate pairs, cellular RSK1 copreci...
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.0805057106
更新日期:2009-06-09 00:00:00
abstract::Ovarian cancer remains the most lethal gynecologic malignancy. We analyzed the mutational landscape of 64 primary, 41 metastatic, and 17 recurrent fresh-frozen tumors from 77 patients along with matched normal DNA, by whole-exome sequencing (WES). We also sequenced 13 pairs of synchronous bilateral ovarian cancer (SBO...
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.1814027116
更新日期:2019-01-08 00:00:00
abstract::Obese fat pads are frequently undervascularized and hypoxic, leading to increased fibrosis, inflammation, and ultimately insulin resistance. We hypothesized that VEGF-A-induced stimulation of angiogenesis enables sustained and sufficient oxygen and nutrient exchange during fat mass expansion, thereby improving adipose...
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.1200447109
更新日期:2012-04-10 00:00:00
abstract::Mutations in the visA gene of Escherichia coli cause the mutant bacteria to die upon illumination with visible light. We confirmed genetically that the visA gene is a structural gene for ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1). Since other mutations in the genes involved in the biosynthesis of heme can cur...
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.88.23.10520
更新日期:1991-12-01 00:00:00
abstract::Inward rectifying potassium (Kir) channels participate in regulating potassium concentration (K(+)) in the central nervous system (CNS), including in the retina. We explored the contribution of Kir channels to retinal function by delivering Kir antibodies (Kir-Abs) into the rat eye in vivo to interrupt channel activit...
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.0913472107
更新日期:2010-07-13 00:00:00
abstract::Immunoprecipitation followed by mass spectrometry (IP/MS) has recently emerged as a preferred method in the analysis of protein complex components and cellular protein networks. Targeting endogenous protein complexes of higher eukaryotes, particularly in large-scale efforts, has been challenging due to cellular hetero...
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.0912599106
更新日期:2010-02-09 00:00:00
abstract::Cultured skin fibroblasts from patients with Menkes disease, an X-linked disorder involving a defect in copper metabolism, were analyzed for copper concentration by means of atomic absorption spectrophotometry. These cultures consistently exhibited elevated copper concentrations (mean = 335.5 ng of copper per mg of pr...
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.73.2.604
更新日期:1976-02-01 00:00:00
abstract::Our understanding of membranes and membrane lipid function has lagged far behind that of nucleic acids and proteins, largely because it is difficult to manipulate cellular membrane lipid composition. To help solve this problem, we show that methyl-α-cyclodextrin (MαCD)-catalyzed lipid exchange can be used to maximally...
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.1610705113
更新日期:2016-12-06 00:00:00
abstract::Perhydrohistrionicotoxin, at concentrations of 10(-12)-10(-7) M, depressed the current generated by iontophoretic application of acetylcholine to endplate regions of soleus and extensor digitorum longus muscles of rats. However, no changes in the amplitude or time course of spontaneous miniature endplate potentials or...
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.75.3.1596
更新日期:1978-03-01 00:00:00
abstract::Transforming growth factor beta (TGF-beta) signals through a receptor complex containing the type I (TGF-beta RI) and type II (TGF-beta RII) receptors. We describe here biochemical studies on early events in the TGF-beta signaling pathways. TGF-beta RII is highly phosphorylated when expressed alone in COS-1 cells; its...
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.92.5.1565
更新日期:1995-02-28 00:00:00
abstract::We study static and dynamical properties that distinguish 2D crystals constrained to lie on a curved substrate from their flat-space counterparts. A generic mechanism of dislocation unbinding in the presence of varying Gaussian curvature is presented in the context of a model surface amenable to full analytical treatm...
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.0602755103
更新日期:2006-08-15 00:00:00
abstract::Glucocorticoids rapidly and completely inhibit intracellular plasminogen activator activity in rat hepatoma cells, as assayed by the solubilization of 125I-labeled fibrin. Experiments in which extracts of dexamethasone-treated cells are mixed with extracts of control cells demonstrate an inhibitor of protease activity...
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.75.12.6130
更新日期:1978-12-01 00:00:00
abstract::The rapid worldwide spread of severe acute respiratory syndrome demonstrated the potential threat an infectious disease poses in a closely interconnected and interdependent world. Here we introduce a probabilistic model that describes the worldwide spread of infectious diseases and demonstrate that a forecast of the 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.0308344101
更新日期:2004-10-19 00:00:00
abstract::The genomic basis of primate phenotypic uniqueness remains obscure, despite increasing genome and transcriptome sequence data availability. Although factors such as segmental duplications and positive selection have received much attention as potential drivers of primate phenotypes, single-copy primate-specific genes ...
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.0904569106
更新日期:2009-07-21 00:00:00
abstract::To maintain genome stability, cells with damaged DNA must arrest to allow repair of mutations before replication. Although several key components required to elicit this arrest have been discovered, much of the pathway remains elusive. Here we report that pRB acts as a central mediator of the proliferative block induc...
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.95.20.11945
更新日期:1998-09-29 00:00:00
abstract::Somatic copy number variations (CNVs) exist in the brain, but their genesis, prevalence, forms, and biological impact remain unclear, even within experimentally tractable animal models. We combined a transposase-based amplification (TbA) methodology for single-cell whole-genome sequencing with a bioinformatic approach...
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.1812702115
更新日期:2018-10-16 00:00:00
abstract::Intracellular Ca(2+) release in many types of cells is mediated by ryanodine receptor Ca(2+) release channels (RyRCs) that are assembled into two-dimensional paracrystalline arrays in the endoplasmic/sarcoplasmic reticulum. However, the in situ operating mechanism of the RyRC array is unknown. Here, we found that 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.0306157101
更新日期:2004-03-16 00:00:00
abstract::G protein-coupled receptors (GPCRs) play central roles in almost all physiological functions; mutations in GPCRs are responsible for more than 30 disorders. There is a great deal of information about GPCR structure but little information that directly relates structure to protein trafficking or to activation. The gona...
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.0914261107
更新日期:2010-03-02 00:00:00
abstract::Somatic crossing over in flies heterozygous for a dominant Minute mutant may result in two cells, homozygous for wild type and Minute, respectively. If both cells took part in development, a twin spot of two genotypes, different from the rest of the body, would result. Two-hundred wild type spots were found, none of 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.68.2.329
更新日期:1971-02-01 00:00:00