Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes.

Abstract:

:The principal methyl donor of the cell, S-adenosylmethionine (SAMe), is produced by the highly conserved family of methionine adenosyltranferases (MATs) via an ATP-driven process. These enzymes play an important role in the preservation of life, and their dysregulation has been tightly linked to liver and colon cancers. We present crystal structures of human MATα2 containing various bound ligands, providing a "structural movie" of the catalytic steps. High- to atomic-resolution structures reveal the structural elements of the enzyme involved in utilization of the substrates methionine and adenosine and in formation of the product SAMe. MAT enzymes are also able to produce S-adenosylethionine (SAE) from substrate ethionine. Ethionine, an S-ethyl analog of the amino acid methionine, is known to induce steatosis and pancreatitis. We show that SAE occupies the active site in a manner similar to SAMe, confirming that ethionine also uses the same catalytic site to form the product SAE.

authors

Murray B,Antonyuk SV,Marina A,Lu SC,Mato JM,Hasnain SS,Rojas AL

doi

10.1073/pnas.1510959113

subject

Has Abstract

pub_date

2016-02-23 00:00:00

pages

2104-9

issue

8

eissn

0027-8424

issn

1091-6490

pii

1510959113

journal_volume

113

pub_type

杂志文章
  • Mutation in sorghum LOW GERMINATION STIMULANT 1 alters strigolactones and causes Striga resistance.

    abstract::Striga is a major biotic constraint to sorghum production in semiarid tropical Africa and Asia. Genetic resistance to this parasitic weed is the most economically feasible control measure. Mutant alleles at the LGS1 (LOW GERMINATION STIMULANT 1) locus drastically reduce Striga germination stimulant activity. We provid...

    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.1618965114

    authors: Gobena D,Shimels M,Rich PJ,Ruyter-Spira C,Bouwmeester H,Kanuganti S,Mengiste T,Ejeta G

    更新日期:2017-04-25 00:00:00

  • Transporters of arsenite in rice and their role in arsenic accumulation in rice grain.

    abstract::Arsenic poisoning affects millions of people worldwide. Human arsenic intake from rice consumption can be substantial because rice is particularly efficient in assimilating arsenic from paddy soils, although the mechanism has not been elucidated. Here we report that two different types of transporters mediate transpor...

    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.0802361105

    authors: Ma JF,Yamaji N,Mitani N,Xu XY,Su YH,McGrath SP,Zhao FJ

    更新日期:2008-07-22 00:00:00

  • Actively transcribed genes in the raf oncogene group, located on the X chromosome in mouse and human.

    abstract::Murine and human cDNAs, related to but distinct from c-raf-1, have been isolated and designated mA-raf and hA-raf, respectively. The mA-raf and hA-raf cDNAs detect the same murine and human fragments in Southern blots of restriction enzyme-cleaved murine and human cellular DNA. The murine restriction enzyme fragments ...

    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.83.11.3934

    authors: Huebner K,ar-Rushdi A,Griffin CA,Isobe M,Kozak C,Emanuel BS,Nagarajan L,Cleveland JL,Bonner TI,Goldsborough MD

    更新日期:1986-06-01 00:00:00

  • Molecular cloning of the flavin-containing monooxygenase (form II) cDNA from adult human liver.

    abstract::Complementary DNA (cDNA) clones encoding the adult human liver flavin-containing monooxygenase (FMO; dimethylaniline N-oxidase, EC 1.14.13.8) were isolated from lambda gt10 and lambda gt11 libraries. The cDNA libraries were screened with three synthetic 36-mer oligonucleotide probes derived from the nucleic acid seque...

    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.89.5.1685

    authors: Lomri N,Gu Q,Cashman JR

    更新日期:1992-03-01 00:00:00

  • Control of bud activation by an auxin transport switch.

    abstract::In many plant species only a small proportion of buds yield branches. Both the timing and extent of bud activation are tightly regulated to produce specific branching architectures. For example, the primary shoot apex can inhibit the activation of lateral buds. This process is termed apical dominance and is dependent ...

    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.0906696106

    authors: Prusinkiewicz P,Crawford S,Smith RS,Ljung K,Bennett T,Ongaro V,Leyser O

    更新日期:2009-10-13 00:00:00

  • Insulin exerts metabolic and growth-promoting effects by a direct action on the liver in vivo: clarification of the functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver.

    abstract::The functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver has not been established. Previous studies indicated that insulin does not acutely regulate glucose metabolism by a direct hepatic effect. More recent observations suggest that the role of insulin in r...

    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.84.20.7300

    authors: Griffen SC,Russell SM,Katz LS,Nicoll CS

    更新日期:1987-10-01 00:00:00

  • Spatiotemporal expression patterns of chicken ovalbumin upstream promoter-transcription factors in the developing mouse central nervous system: evidence for a role in segmental patterning of the diencephalon.

    abstract::Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) genes encode transcription factors belonging to the orphan subfamily of the steroid/thyroid hormone receptor superfamily. Two COUP-TF counterparts have been cloned from mouse. In an attempt to study the function of these genes in the developing central...

    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.91.10.4451

    authors: Qiu Y,Cooney AJ,Kuratani S,DeMayo FJ,Tsai SY,Tsai MJ

    更新日期:1994-05-10 00:00:00

  • Direct effects of 17 beta-estradiol on trabecular bone in ovariectomized rats.

    abstract::High-affinity nuclear binding sites for 17 beta-estradiol (17 beta E2) were recently found in bone cells; however, the mechanism by which estrogen exerts its effect on bone in vivo is still unknown. To study if estrogen acts on bone directly, we used an experimental model in which test substances are infused locally 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.87.6.2172

    authors: Takano-Yamamoto T,Rodan GA

    更新日期:1990-03-01 00:00:00

  • Circular dichroism and molecular modeling yield a structure for the complex of human immunodeficiency virus type 1 trans-activation response RNA and the binding region of Tat, the trans-acting transcriptional activator.

    abstract::Transcription in the human immunodeficiency virus type 1 (HIV-1) retrovirus is regulated by binding the viral Tat protein (trans-acting transcriptional activator) to the trans-activation response (TAR) RNA sequence. Here, vacuum UV circular dichroism (VUV-CD) is used to study the structure of TAR and its complex with ...

    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.89.20.9734

    authors: Loret EP,Georgel P,Johnson WC Jr,Ho PS

    更新日期:1992-10-15 00:00:00

  • Alternative processing of bovine growth hormone mRNA: nonsplicing of the final intron predicts a high molecular weight variant of bovine growth hormone.

    abstract::We have detected a variant species of bovine growth hormone mRNA in bovine pituitary tissue and in a stably transfected bovine growth hormone-producing cell line. Analysis of this variant mRNA indicated that the last intervening sequence (intron D) had not been removed by splicing. Inspection of the sequence of intron...

    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.84.9.2673

    authors: Hampson RK,Rottman FM

    更新日期:1987-05-01 00:00:00

  • Local demographic changes and US presidential voting, 2012 to 2016.

    abstract::Immigration and demographic change have become highly salient in American politics, partly because of the 2016 campaign of Donald Trump. Previous research indicates that local influxes of immigrants or unfamiliar ethnic groups can generate threatened responses, but has either focused on nonelectoral outcomes or analyz...

    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.1909202116

    authors: Hill SJ,Hopkins DJ,Huber GA

    更新日期:2019-12-10 00:00:00

  • RNAs in Epstein-Barr virions control early steps of infection.

    abstract::Herpesviruses are dsDNA viruses, but their virions may additionally contain RNAs that can be transduced to recipient cells. The biological functions of herpes virion RNA species are unknown. Here we address this issue for EBV, a widespread human herpesvirus with oncogenic potential. We show that EBV-derived particles ...

    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.1115906109

    authors: Jochum S,Ruiss R,Moosmann A,Hammerschmidt W,Zeidler R

    更新日期:2012-05-22 00:00:00

  • Quon 3D language for quantum information.

    abstract::We present a 3D topological picture-language for quantum information. Our approach combines charged excitations carried by strings, with topological properties that arise from embedding the strings in the interior of a 3D manifold with boundary. A quon is a composite that acts as a particle. Specifically, a quon is 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.1621345114

    authors: Liu Z,Wozniakowski A,Jaffe AM

    更新日期:2017-03-07 00:00:00

  • From the Cover: Antarctic climate signature in the Greenland ice core record.

    abstract::A numerical algorithm is applied to the Greenland Ice Sheet Project 2 (GISP2) dust record from Greenland to remove the abrupt changes in dust flux associated with the Dansgaard-Oeschger (D-O) oscillations of the last glacial period. The procedure is based on the assumption that the rapid changes in dust are associated...

    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.0708494104

    authors: Barker S,Knorr G

    更新日期:2007-10-30 00:00:00

  • Dynein pulls microtubules without rotating its stalk.

    abstract::Dynein is a microtubule motor that powers motility of cilia and flagella. There is evidence that the relative sliding of the doublet microtubules is due to a conformational change in the motor domain that moves a microtubule bound to the end of an extension known as the stalk. A predominant model for the movement invo...

    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.0808194105

    authors: Ueno H,Yasunaga T,Shingyoji C,Hirose K

    更新日期:2008-12-16 00:00:00

  • Human G(salpha) mutant causes pseudohypoparathyroidism type Ia/neonatal diarrhea, a potential cell-specific role of the palmitoylation cycle.

    abstract::Pseudohypoparathyroidism type Ia (PHP-Ia) results from the loss of one allele of G(salpha), causing resistance to parathyroid hormone and other hormones that transduce signals via G(s). Most G(salpha)mutations cause the complete loss of protein expression, but some cause loss of function only, and these have provided ...

    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.0708561104

    authors: Makita N,Sato J,Rondard P,Fukamachi H,Yuasa Y,Aldred MA,Hashimoto M,Fujita T,Iiri T

    更新日期:2007-10-30 00:00:00

  • Activity-based probes for proteomic profiling of histone deacetylase complexes.

    abstract::Histone deacetylases (HDACs) are key regulators of gene expression that require assembly into larger protein complexes for activity. Efforts to understand how associated proteins modulate the function of HDACs would benefit from new technologies that evaluate HDAC activity in native biological systems. Here, we descri...

    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.0608659104

    authors: Salisbury CM,Cravatt BF

    更新日期:2007-01-23 00:00:00

  • Reconstitution of Ir genes, Ia antigens, and mixed lymphocyte reaction determinants by gene complementation.

    abstract::By using clones of murine T cells reactive with alloantigens as well as soluble antigens, it has been possible to demonstrate that Ia antigens, Ir gene phenomena (defined as the ability of immune T cells to recognize antigen), and mixed lymphocyte reaction (MLR)-stimulating determinants encoded within the I-A subregio...

    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.78.3.1853

    authors: Fathman CG,Kimoto M,Melvold R,David CS

    更新日期:1981-03-01 00:00:00

  • "...the tyranny of the lattice...".

    abstract::A systematic comparison of crystal structures of nine different B-DNA dodecamers, in three different space groups, with and without A-tracts, shows that crystal packing or lattice forces are of secondary importance for helix axis bending, minor-groove width, and propeller twist. While other local helix parameters may ...

    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.91.9.3579

    authors: Dickerson RE,Goodsell DS,Neidle S

    更新日期:1994-04-26 00:00:00

  • Colonization of the Krakatau Islands by vertebrates: equilibrium, succession, and possible delayed extinction.

    abstract::MacArthur and Wilson [MacArthur, R. H. & Wilson, E. O. (1967) The Theory of Island Biogeography (Princeton Univ. Press, Princeton, NJ)] used the rate of recolonization of the Krakatau Islands (sterilized in the cataclysmic 1883 eruption) by birds and vascular plants to test their equilibrium model of immigration 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.85.2.515

    authors: Thornton IW,Zann RA,Rawlinson PA,Tidemann CR,Adikerana AS,Widjoya AH

    更新日期:1988-01-01 00:00:00

  • Compositional heterogeneity of human heterochromatin.

    abstract::When human genome was fractionated by thermal elution chromatography, repetitious DNA was found in every arbitrary temperature segment. When these repetitious DNA families were used for in situ hybridization, the following conclusions were evident: (a) Unlike the case of mouse, where essentially all centromeric 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.69.6.1464

    authors: Hsu TC,Arrighi FE,Saunders GF

    更新日期:1972-06-01 00:00:00

  • Nongenetic origins of cell-to-cell variability in B lymphocyte proliferation.

    abstract::Rapid antibody production in response to invading pathogens requires the dramatic expansion of pathogen-derived antigen-specific B lymphocyte populations. Whether B cell population dynamics are based on stochastic competition between competing cell fates, as in the development of competence by the bacterium Bacillus 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.1715639115

    authors: Mitchell S,Roy K,Zangle TA,Hoffmann A

    更新日期:2018-03-20 00:00:00

  • Bacterial growth and motility in sub-micron constrictions.

    abstract::In many naturally occurring habitats, bacteria live in micrometer-size confined spaces. Although bacterial growth and motility in such constrictions is of great interest to fields as varied as soil microbiology, water purification, and biomedical research, quantitative studies of the effects of confinement on bacteria...

    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.0907542106

    authors: Männik J,Driessen R,Galajda P,Keymer JE,Dekker C

    更新日期:2009-09-01 00:00:00

  • The pre-S domain of the large viral envelope protein determines host range in avian hepatitis B viruses.

    abstract::In addition to their well-recognized hepatotropism, all hepatitis B viruses (HBVs) display marked species specificity, growing poorly or not at all in species other than those closely related to their natural hosts. We have examined the molecular basis for this narrow host range, using duck HBV (DHBV) and heron HBV (H...

    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.92.14.6259

    authors: Ishikawa T,Ganem D

    更新日期:1995-07-03 00:00:00

  • Germ-line chimerism and paternal care in marmosets (Callithrix kuhlii).

    abstract::The formation of viable genetic chimeras in mammals through the transfer of cells between siblings in utero is rare. Using microsatellite DNA markers, we show here that chimerism in marmoset (Callithrix kuhlii) twins is not limited to blood-derived hematopoietic tissues as was previously described. All somatic tissue ...

    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.0607426104

    authors: Ross CN,French JA,Ortí G

    更新日期:2007-04-10 00:00:00

  • Adaptive climatic molecular evolution in wild barley at the Isa defense locus.

    abstract::Wild barley (Hordeum spontaneum) represents a significant genetic resource for crop improvement in barley (Hordeum vulgare) and for the study of the evolution and domestication of plant populations. The Isa gene from barley has a putative role in plant defense. This gene encodes a bifunctional alpha-amylase/subtilisin...

    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.0611226104

    authors: Cronin JK,Bundock PC,Henry RJ,Nevo E

    更新日期:2007-02-20 00:00:00

  • Mechanism of calcium current modulation underlying presynaptic facilitation and behavioral sensitization in Aplysia.

    abstract::Behavioral sensitization of the gill-withdrawal reflex of Aplysia is caused by presynaptic facilitation at the synapses of the mechanoreceptor sensory neurons of the reflex onto the motor neurons and interneurons. The presynaptic facilitation has been shown to be simulated by serotonin (the putative presynaptic facili...

    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.77.11.6912

    authors: Klein M,Kandel ER

    更新日期:1980-11-01 00:00:00

  • Occurrence in Mexico, 1998-2008, of Vibrio cholerae CTX+ El Tor carrying an additional truncated CTX prophage.

    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

    authors: Alam M,Rashed SM,Mannan SB,Islam T,Lizarraga-Partida ML,Delgado G,Morales-Espinosa R,Mendez JL,Navarro A,Watanabe H,Ohnishi M,Hasan NA,Huq A,Sack RB,Colwell RR,Cravioto A

    更新日期:2014-07-08 00:00:00

  • Curved DNA: design, synthesis, and circularization.

    abstract::Curved DNA molecules and unusually small circles have been obtained by ligation of synthetic 21-base precursors: (sequence in text). The ligation resulted in the formation of double-stranded oligo-(precursor)s possessing a strong 10.5-base-pair (bp) periodicity of the runs of adenines. Two-dimensional polyacrylamide 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.83.4.862

    authors: Ulanovsky L,Bodner M,Trifonov EN,Choder M

    更新日期:1986-02-01 00:00:00

  • Imaging burst kinetics and spatial coordination during serial killing by single natural killer cells.

    abstract::Cytotoxic lymphocytes eliminate virus-infected and cancerous cells by immune recognition and killing through the perforin-granzyme pathway. Traditional killing assays measure average target cell lysis at fixed times and high effector:target ratios. Such assays obscure kinetic details that might reveal novel physiology...

    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.1221312110

    authors: Choi PJ,Mitchison TJ

    更新日期:2013-04-16 00:00:00