Abstract:
:Human cytosolic NADP-IDH (IDH1) has recently been found to be involved in tumorigenesis. Notably, the tumor-derived IDH1 mutations identified so far mainly occur at Arg132, and mutation R132H is the most prevalent one. This mutation impairs the oxidative IDH activity of the enzyme, but renders a new reduction function of converting α-ketoglutarate (αKG) to 2-hydroxyglutarate. Here, we report the structures of the R132H mutant IDH1 with and without isocitrate (ICT) bound. The structural data together with mutagenesis and biochemical data reveal a previously undefined initial ICT-binding state and demonstrate that IDH activity requires a conformational change to a closed pre-transition state. Arg132 plays multiple functional roles in the catalytic reaction; in particular, the R132H mutation hinders the conformational changes from the initial ICT-binding state to the pre-transition state, leading to the impairment of the IDH activity. Our results describe for the first time that there is an intermediate conformation that corresponds to an initial ICT-binding state and that the R132H mutation can trap the enzyme in this conformation, therefore shedding light on the molecular mechanism of the "off switch" of the potentially tumor-suppressive IDH activity. Furthermore, we proved the necessity of Tyr139 for the gained αKG reduction activity and propose that Tyr139 may play a vital role by compensating the increased negative charge on the C2 atom of αKG during the transfer of a hydride anion from NADPH to αKG, which provides new insights into the mechanism of the "on switch" of the hypothetically oncogenic reduction activity of IDH1 by this mutation.
journal_name
Cell Resjournal_title
Cell researchauthors
Yang B,Zhong C,Peng Y,Lai Z,Ding Jdoi
10.1038/cr.2010.145subject
Has Abstractpub_date
2010-11-01 00:00:00pages
1188-200issue
11eissn
1001-0602issn
1748-7838pii
cr2010145journal_volume
20pub_type
杂志文章相关文献
CELL RESEARCH文献大全abstract::Recent evidence indicates that codon optimality is a broad determinant of mRNA stability. A study by Radhakrishnan et al. in Cell raises the possibility that the conserved DEAD-box protein Dhh1 underlies the phenomenon. ...
journal_title:Cell research
pub_type: 评论,杂志文章
doi:10.1038/cr.2016.127
更新日期:2016-12-01 00:00:00
abstract::Plant reproduction is initiated by the specification of sporocytes that form haploid spores through meiosis. A new study in Arabidopsis published in Cell Research shows how the product of sporocyteless/nozzle, a key gene in this process, partners with co-repressors and transcription factors to promote spore formation,...
journal_title:Cell research
pub_type: 评论,杂志文章
doi:10.1038/cr.2014.164
更新日期:2015-01-01 00:00:00
abstract::Previously, mouse bone marrow-derived stem cells (MSC) treated with the unspecific DNA methyltransferase inhibitor 5-azacytidine were reported to differentiate into cardiomyocytes. The aim of the present study was to investigate the efficiency of a similar differentiation strategy in human mononuclear cells obtained f...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/sj.cr.7310116
更新日期:2006-12-01 00:00:00
abstract::Two distinct nuclear factor κB (NFκB) signaling pathways have been described; the canonical pathway that mediates inflammatory responses, and the non-canonical pathway that is involved in immune cell differentiation and maturation and secondary lymphoid organogenesis. The former is dependent on the IκB kinase adaptor ...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/cr.2010.161
更新日期:2011-01-01 00:00:00
abstract::Vascular integrity helps maintain brain microenvironment homeostasis, which is critical for the normal development and function of the central nervous system. It is known that neural cells can regulate brain vascular integrity. However, due to the high complexity of neurovascular interactions involved, understanding o...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2017.62
更新日期:2017-07-01 00:00:00
abstract::Mechanical deformability is known to increase during cancer progression. Now Ma et al. identify a therapeutic strategy that targets deformable cells by microparticle-based drug delivery. ...
journal_title:Cell research
pub_type: 评论,杂志文章
doi:10.1038/cr.2016.54
更新日期:2016-06-01 00:00:00
abstract::Polyamines are implicated in regulating various developmental processes in plants, but their exact roles and how they govern these processes still remain elusive. We report here an Arabidopsis bushy and dwarf mutant, bud2, which results from the complete deletion of one member of the small gene family that encodes S-a...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/sj.cr.7310056
更新日期:2006-05-01 00:00:00
abstract::Beta adrenergic receptors (βARs) mediate physiologic responses to the catecholamines epinephrine and norepinephrine released by the sympathetic nervous system. While the hormone epinephrine binds β1AR and β2AR with similar affinity, the smaller neurotransmitter norepinephrine is approximately tenfold selective for the...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/s41422-020-00424-2
更新日期:2020-10-22 00:00:00
abstract::Accumulating evidence indicates that the mesenchymal-epithelial transition (MET) and epithelial-mesenchymal transition (EMT) are basic mechanisms for cell fate conversion and may help us understand both physiologic and pathologic processes such as development and carcinogenesis. Here, we further suggest that mammalian...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2014.93
更新日期:2014-10-01 00:00:00
abstract::NF-κBs are a family of transcription factors that control a number of essential cellular functions including immune responses, cell proliferation and antiapoptosis. NF-κB activities are tightly regulated through upstream signaling molecules and downstream feedback loops. In this review, structural discoveries in the N...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/cr.2010.171
更新日期:2011-01-01 00:00:00
abstract::The Hippo pathway is a signal transduction pathway that regulates organ growth, stem cell biology, regeneration and cancer. Three recent proteomic studies with Hippo pathway components uncovered extensive networks of interacting proteins revealing novel connections to cell-cell junctions, regulation by vesicle traffic...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2014.6
更新日期:2014-02-01 00:00:00
abstract::Leaf morphogenesis requires the establishment of adaxial-abaxial polarity after primordium initiation from the shoot apical meristem (SAM). Several families of transcription factors are known to play critical roles in promoting adaxial or abaxial leaf fate. Recently, post-transcriptional gene silencing pathways have b...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/cr.2007.45
更新日期:2007-06-01 00:00:00
abstract::Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and has been shown to be closely associated with various malignancies. Here, we present a complete atomic model of EBV, including the icosahedral capsid, the dodecameric portal and the capsid-associated tegument complex (CATC). Our in situ porta...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/s41422-020-0363-0
更新日期:2020-10-01 00:00:00
abstract::This investigation reports a protocol for transfer and expression of foreign chimeric genes in loblolly pine (Pinus taeda L.). Transformation was achieved by co-cultivation of mature zygotic embryos with Agrobacterium tumefaciens strain LBA4404 which harbored a binary vector (pBI121) including genes for beta-glucuroni...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/sj.cr.7290092
更新日期:2001-09-01 00:00:00
abstract::There are remarkable disparities among patients of different races with prostate cancer; however, the mechanism underlying this difference remains unclear. Here, we present a comprehensive landscape of the transcriptome profiles of 14 primary prostate cancers and their paired normal counterparts from the Chinese popul...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2012.30
更新日期:2012-05-01 00:00:00
abstract::High-density lipoproteins (HDLs) have been well established to protect against the development of atherosclerotic cardiovascular disease. It has become apparent that in addition to the promotion of reverse cholesterol transport, HDLs possess a number of additional functional properties that may contribute to their ben...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/sj.cr.7310097
更新日期:2006-10-01 00:00:00
abstract::Type I interferon (IFN) production plays pivotal roles in host antiviral innate immune responses, but an excessive production of type I IFN leads to the development of immunopathological conditions. Investigations on the regulatory mechanisms underlying host type I IFN production are currently of great interest. Here,...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2015.108
更新日期:2015-10-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Cell research
pub_type: 已发布勘误
doi:10.1038/s41422-020-0311-z
更新日期:2020-06-01 00:00:00
abstract::Tumor initiation and growth depend on its microenvironment in which cancer-associated fibroblasts (CAFs) in tumor stroma play an important role. Prostaglandin E2 (PGE2) and interleukin (IL)-6 signal pathways are involved in the crosstalk between tumor and stromal cells. However, how PGE2-mediated signaling modulates t...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2015.51
更新日期:2015-05-01 00:00:00
abstract::The nucleotide sequence deduced from the amino acid sequence of the scorpion insectotoxin AaIT was chemically synthesized and was expressed in Escherichia coli. The authenticity of this in vitro expressed peptide was confirmed by N-terminal peptide sequencing. Two groups of bioassays, artificial diet incorporation ass...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/sj.cr.7290120
更新日期:2002-06-01 00:00:00
abstract::Intermittent fasting (IF) has been shown to promote metabolic health in several organisms. Two recent papers show that IF induces white adipose tissue beiging and increases thermogenesis, which improves metabolic health in mice. ...
journal_title:Cell research
pub_type: 评论,杂志文章
doi:10.1038/cr.2017.130
更新日期:2017-11-01 00:00:00
abstract::Various factors/pathways including hormonal regulation have been suggested to control herpes simplex virus type 1 (HSV-1) latency and reactivation. Our computer analysis identified a DNA repeat containing thyroid hormone-responsive elements (TRE) in the regulatory region of HSV-1 latency-associated transcript (LAT). T...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2010.50
更新日期:2010-05-01 00:00:00
abstract::DNA double-strand breaks (DSBs) are introduced in cells by ionizing radiation and reactive oxygen species. In addition, they are commonly generated during V(D)J recombination, an essential aspect of the developing immune system. Failure to effectively repair these DSBs can result in chromosome breakage, cell death, on...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/cr.2008.3
更新日期:2008-01-01 00:00:00
abstract::Kinesins are microtubule-based motors involved in various intracellular transports. Neurons, flagellated cells, and pigment cells have been traditionally used as model systems to study the cellular functions of kinesins. Here, we report silkworm posterior silkgland (PSG), specialized cells with an extensive endomembra...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2010.47
更新日期:2010-06-01 00:00:00
abstract::In vivo genome editing represents a powerful strategy for both understanding basic biology and treating inherited diseases. However, it remains a challenge to develop universal and efficient in vivo genome-editing tools for tissues that comprise diverse cell types in either a dividing or non-dividing state. Here, we d...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/s41422-019-0213-0
更新日期:2019-10-01 00:00:00
abstract::Brassinosteroids (BRs) are essential steroid hormones that have crucial roles in plant growth and development. BRs are perceived by the cell-surface receptor-like kinase brassinosteroid insensitive 1 (BRI1). In the absence of BRs, the cytosolic kinase domain (KD) of BRI1 is inhibited by its auto-inhibitory carboxyl te...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2014.132
更新日期:2014-11-01 00:00:00
abstract::Long-range chromatin interactions between enhancers and promoters are essential for transcription of many developmentally controlled genes in mammals and other metazoans. Currently, the exact mechanisms that connect distal enhancers to their specific target promoters remain to be fully elucidated. Here, we show that t...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2018.1
更新日期:2018-02-01 00:00:00
abstract::DNA hydrolysis is a biochemical process often associated with different forms of cell death, including apoptosis. In a recent paper published in Cell Discovery, Du et al. report that synaptic acetylcholinesterase (AChE-S) shows an unexpected enzymatic activity as DNase switched on after cytotoxic insults. ...
journal_title:Cell research
pub_type: 评论,杂志文章
doi:10.1038/cr.2015.52
更新日期:2015-06-01 00:00:00
abstract::Paramyxoviruses evade antiviral immune response using a small nonstructural protein, V, which binds to the host dsRNA sensor MDA5 and prevents it from activating the interferon signaling pathway. A recent crystal structure of the V protein in complex with MDA5, published in Science, revealed that V disrupts the struct...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2013.32
更新日期:2013-06-01 00:00:00
abstract::The 5' fragment (1 647 bp) of the cotton glucuronosyltransferase gene (GhGlcAT1) was transcriptionally fused to the beta-glucuronidase (GUS) gene, and functionally analyzed for important regulatory regions controlling gene expression in transgenic tobacco plants. GUS activity analysis revealed that the full-length pro...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/sj.cr.7310119
更新日期:2007-02-01 00:00:00