Abstract:
:l-Serine biosynthesis, a crucial metabolic process in most domains of life, is initiated by d-3-phosphoglycerate (d-3-PG) dehydrogenation, a thermodynamically unfavorable reaction catalyzed by d-3-PG dehydrogenase (SerA). d-2-Hydroxyglutarate (d-2-HG) is traditionally viewed as an abnormal metabolite associated with cancer and neurometabolic disorders. Here, we reveal that bacterial anabolism and catabolism of d-2-HG are involved in l-serine biosynthesis in Pseudomonas stutzeri A1501 and Pseudomonas aeruginosa PAO1. SerA catalyzes the stereospecific reduction of 2-ketoglutarate (2-KG) to d-2-HG, responsible for the major production of d-2-HG in vivo. SerA combines the energetically favorable reaction of d-2-HG production to overcome the thermodynamic barrier of d-3-PG dehydrogenation. We identified a bacterial d-2-HG dehydrogenase (D2HGDH), a flavin adenine dinucleotide (FAD)-dependent enzyme, that converts d-2-HG back to 2-KG. Electron transfer flavoprotein (ETF) and ETF-ubiquinone oxidoreductase (ETFQO) are also essential in d-2-HG metabolism through their capacity to transfer electrons from D2HGDH. Furthermore, while the mutant with D2HGDH deletion displayed decreased growth, the defect was rescued by adding l-serine, suggesting that the D2HGDH is functionally tied to l-serine synthesis. Substantial flux flows through d-2-HG, being produced by SerA and removed by D2HGDH, ETF, and ETFQO, maintaining d-2-HG homeostasis. Overall, our results uncover that d-2-HG-mediated coupling between SerA and D2HGDH drives bacterial l-serine synthesis.
journal_name
Proc Natl Acad Sci U S Aauthors
Zhang W,Zhang M,Gao C,Zhang Y,Ge Y,Guo S,Guo X,Zhou Z,Liu Q,Zhang Y,Ma C,Tao F,Xu Pdoi
10.1073/pnas.1619034114subject
Has Abstractpub_date
2017-09-05 00:00:00pages
E7574-E7582issue
36eissn
0027-8424issn
1091-6490pii
1619034114journal_volume
114pub_type
杂志文章abstract::Growth inhibition assays indicated that the IC50 values for methotrexate (MTX) and 5-fluorodeoxyuridine (FdUrd) in HS-18, a liposarcoma cell line lacking retinoblastoma protein (pRB), and SaOS-2, an osteosarcoma cell line with a truncated and nonfunctional pRB, were 10- to 12-fold and 4- to 11-fold higher, respectivel...
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.92.22.10436
更新日期:1995-10-24 00:00:00
abstract::One of the greatest challenges in contemporary condensed matter physics is to ascertain whether the formation of glasses from liquids is fundamentally thermodynamic or dynamic in origin. Although the thermodynamic paradigm has dominated theoretical research for decades, the purely kinetic perspective of the dynamical ...
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.1413384111
更新日期:2014-10-28 00:00:00
abstract::Previous work has uncovered the existence of an Escherichia coli locus, groE, that is essential for bacterial growth, lambda phage and T4 phage head morphogenesis, and T5 phage tail assembly. Our genetic and biochemical analyses of lambda groE+ transducing phages and their deletion and point mutant derivatives show th...
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.78.3.1629
更新日期:1981-03-01 00:00:00
abstract::Poly(ADP ribose) polymerase inhibitors (PARPi) have efficacy in triple negative breast (TNBC) and ovarian cancers (OCs) harboring BRCA mutations, generating homologous recombination deficiencies (HRDs). DNA methyltransferase inhibitors (DNMTi) increase PARP trapping and reprogram the DNA damage response to generate HR...
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.2003499117
更新日期:2020-07-28 00:00:00
abstract::Social insects are promising new models in aging research. Within single colonies, longevity differences of several magnitudes exist that can be found elsewhere only between different species. Reproducing queens (and, in termites, also kings) can live for several decades, whereas sterile workers often have a lifespan ...
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.1804046115
更新日期:2018-05-22 00:00:00
abstract::The synthesis of the proteins laminin and collagen IV is stimulated approximately equal to 20-fold in F9 mouse teratocarcinoma stem cells after treatment of the cells with retinoic acid and N6, O2'-dibutyryl-cAMP (Bt2cAMP). A cDNA library from F9 cells treated with retinoic acid, Bt2cAMP, and theophylline (F9-R + DBC ...
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.80.19.5880
更新日期:1983-10-01 00:00:00
abstract::Neurotrophins are potent survival factors for developing and injured neurons. However, they are not being used to treat neurodegenerative diseases because of difficulties in administration and numerous side effects that have been encountered in previous clinical trials. Their biological activities use Trk (tropomyosin...
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.0705267104
更新日期:2007-10-23 00:00:00
abstract::In the coming century, anthropogenic climate change will threaten the persistence of restricted endemic species, complicating conservation planning. Although most efforts to quantify potential shifts in species' ranges use global climate model (GCM) output, regional climate model (RCM) output may be better suited to 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.0501427102
更新日期:2005-11-08 00:00:00
abstract::Necessary conditions are derived for a spherical vortex in a perfect fluid to be stationary in the case when the velocities depend on a single surface harmonic. The motion is indeterminate unless an additional condition is imposed. In the case when this condition is incompressibility, the equations are solved, yieldin...
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.69.9.2460
更新日期:1972-09-01 00:00:00
abstract::After prolonged exposure to ascorbate, collagen synthesis in cultured human skin fibroblasts increased approximately 8-fold with no significant change in synthesis of noncollagen protein. This effect of ascorbate appears to be unrelated to its cofactor function in collagen hydroxylation. The collagenous protein secret...
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.78.5.2879
更新日期:1981-05-01 00:00:00
abstract::We explore the question of what are the best ligands for macromolecular targets. A survey of experimental data on a large number of the strongest-binding ligands indicates that the free energy of binding increases with the number of nonhydrogen atoms with an initial slope of approximately -1.5 kcal/mol (1 cal = 4.18 J...
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.96.18.9997
更新日期:1999-08-31 00:00:00
abstract::Photoperiodic control of testis growth in Passer domesticus (house sparrow) is mediated entirely by extraretinal photoreceptors in the brain. The eyes do not participate in photoperiodically significant photoreception. Removal of the pineal organ does not affect either the response to light or, to a first approximatio...
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.67.1.320
更新日期:1970-09-01 00:00:00
abstract::Real-life decisions are often repeated. Whether considering taking a job in a new city, or doing something mundane like checking if the stove is off, decisions are frequently revisited even if no new information is available. This mode of behavior takes a particularly pathological form in obsessive-compulsive disorder...
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.2014271117
更新日期:2021-01-05 00:00:00
abstract::A purified EcoRI restriction endonuclease fragment that determines resistance to kanamycin and is incapable of self-replication was used to select autonomously replicating fragments from an EcoRI digest of a Salmonella typhimurium F' plasmid containing the chromosomal region believed to include the S. typhimurium orig...
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.76.7.3097
更新日期:1979-07-01 00:00:00
abstract::In eukaryotes, ubiquitination is an important posttranslational process achieved through a cascade of ubiquitin-activating (E1), conjugating (E2), and ligase (E3) enzymes. Many pathogenic bacteria deliver virulence factors into the host cell that function as E3 ligases. How these bacterial "Trojan horses" integrate in...
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.1115025109
更新日期:2012-02-07 00:00:00
abstract::The highly aggressive character of melanoma makes it an excellent model for probing the mechanisms underlying metastasis, which remains one of the most difficult challenges in treating cancer. We find that miR-182, member of a miRNA cluster in a chromosomal locus (7q31-34) frequently amplified in melanoma, is commonly...
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.0808263106
更新日期:2009-02-10 00:00:00
abstract::Managing excess nutrients remains a major obstacle to improving ecosystem service benefits of urban waters. To inform more ecologically based landscape nutrient management, we compared watershed inputs, outputs, and retention for nitrogen (N) and phosphorus (P) in seven subwatersheds of the Mississippi River in St. Pa...
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.1618536114
更新日期:2017-04-18 00:00:00
abstract::A 16-amino acid residue peptide derived from a consensus motif of natural ferredoxins incorporates a tetranuclear iron sulfur cluster under physiological conditions. Successful assembly of the [4Fe-4S]2+/1+ cluster within a monomeric peptide was demonstrated using size exclusion chromatography, UV-visible, visible CD,...
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.93.26.15041
更新日期:1996-12-24 00:00:00
abstract::Synapse formation at the neuromuscular junction (NMJ) requires an alternatively spliced variant of agrin (Z(+) agrin) that is produced only by neurons. Here, we show that Nova1 and Nova2, neuron-specific splicing factors identified as targets in autoimmune motor disease, are essential regulators of Z(+) agrin. Nova1/N...
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.0813112106
更新日期:2009-03-03 00:00:00
abstract::Although gamma frequency oscillations are common in the brain, their functional contributions to neural computation are not understood. Here we report in vitro electrophysiological recordings to evaluate how noisy gamma frequency oscillatory input interacts with the overall activation level of a neuron to determine th...
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.0803183105
更新日期:2008-06-17 00:00:00
abstract::Photochemical oxidation of aromatic hydrocarbons leads to tropospheric ozone and secondary organic aerosol (SOA) formation, with profound implications for air quality, human health, and climate. Toluene is the most abundant aromatic compound under urban environments, but its detailed chemical oxidation mechanism remai...
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.1705463114
更新日期:2017-08-01 00:00:00
abstract::Nanoparticles are increasingly used in various fields, including biomedicine and electronics. One application utilizes the opacifying effect of nano-TiO(2), which is frequently used as pigment in cosmetics. Although TiO(2) is believed to be biologically inert, an emerging literature reports increased incidence of resp...
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.1008155107
更新日期:2010-11-09 00:00:00
abstract::Previous reports have shown that γδ T cells are important for the elimination of malaria parasites in humans and mice. However, how γδ T cells are involved in protective immunity against blood-stage malaria remains unknown. We infected γδ T-cell-deficient (TCRδ-KO) mice and control wild-type mice with Plasmodium bergh...
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.1204480109
更新日期:2012-07-24 00:00:00
abstract::The redox siblings nitroxyl (HNO) and nitric oxide (NO) have often been assumed to undergo casual redox reactions in biological systems. However, several recent studies have demonstrated distinct pharmacological effects for donors of these two species. Here, infusion of the HNO donor Angeli's salt into normal dogs res...
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.1430507100
更新日期:2003-08-05 00:00:00
abstract::The vegetative development of the maize shoot can be divided into juvenile and adult phases based on the types of leaves produced at different times in shoot development. Models for the regulation of phase change make explicit predictions about when the identity of these types of leaves is determined. To test these mo...
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.180301597
更新日期:2000-09-12 00:00:00
abstract::Pyramidal cells in piriform cortex receive excitatory inputs from two different sources that are segregated onto adjacent segments of their apical dendrites. The present studies show that excitatory postsynaptic potentials (EPSPs) evoked by primary olfactory tract afferents that terminate on distal apical segments dis...
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.83.4.1115
更新日期:1986-02-01 00:00:00
abstract::Toxin-antitoxin systems are found in many bacterial chromosomes and plasmids with roles ranging from plasmid stabilization to biofilm formation and persistence. In these systems, the expression/activity of the toxin is counteracted by an antitoxin, which, in type I systems, is an antisense RNA. While the regulatory me...
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.2016195117
更新日期:2020-12-08 00:00:00
abstract::Hypermutation in immunoglobulin genes produces a high frequency of substitutions of all four bases, which are likely generated by low-fidelity DNA polymerases. Indeed, humans deficient for DNA polymerase (pol) eta have decreased substitutions of A.T base pairs in variable and switch regions. To study the role of pol 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.0501852102
更新日期:2005-06-14 00:00:00
abstract::Classical studies suggest that high-level cognitive decisions (e.g., choosing between financial options) are suboptimal. In contrast, low-level decisions (e.g., choosing where to put your feet on a rocky ridge) appear near-optimal: the perception-cognition gap. Moreover, in classical tasks, people appear to put too mu...
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.1300239110
更新日期:2013-10-01 00:00:00
abstract::In everyday life, a macroscopic valve is a device with a movable control element that regulates the flow of gases or liquids by blocking and opening passageways. Construction of such a device on the nanoscale level requires (i) suitably proportioned movable control elements, (ii) a method for operating them on demand,...
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.0504109102
更新日期:2005-07-19 00:00:00