Mis-annotations of a promising antibiotic target in high-priority gram-negative pathogens.

Abstract:

:The rise of antibiotic resistance combined with the lack of new products entering the market has led to bacterial infections becoming one of the biggest threats to global health. Therefore, there is an urgent need to identify novel antibiotic targets, such as dihydrodipicolinate synthase (DHDPS), an enzyme involved in the production of essential metabolites in cell wall and protein synthesis. Here, we utilised a 7-residue sequence motif to identify mis-annotation of multiple DHDPS genes in the high-priority Gram-negative bacteria Acinetobacter baumannii and Klebsiella pneumoniae. We subsequently confirmed these mis-annotations using a combination of enzyme kinetics and X-ray crystallography. Thus, this study highlights the need to ensure genes encoding promising drug targets, like DHDPS, are annotated correctly, especially for clinically important pathogens. PDB ID: 6UE0.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Impey RE,Lee M,Hawkins DA,Sutton JM,Panjikar S,Perugini MA,Soares da Costa TP

doi

10.1002/1873-3468.13733

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

1453-1463

issue

9

eissn

0014-5793

issn

1873-3468

journal_volume

594

pub_type

杂志文章
  • Amino acid substitutions contributing to α2,6-sialic acid linkage binding specificity of human parainfluenza virus type 3 hemagglutinin-neuraminidase.

    abstract::Human parainfluenza virus type 3 (hPIV3) recognizes both α2,3- and α2,6-linked sialic acids, whereas human parainfluenza virus type 1 (hPIV1) recognizes only α2,3-linked sialic acids. To identify amino acid residues that confer α2,6-linked sialic acid recognition of hPIV3, amino acid residues in or neighboring the sia...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2015.03.036

    authors: Fukushima K,Takahashi T,Ueyama H,Takaguchi M,Ito S,Oishi K,Minami A,Ishitsubo E,Tokiwa H,Takimoto T,Suzuki T

    更新日期:2015-05-08 00:00:00

  • Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases.

    abstract::Incubation of rat skeletal muscle mitochondria with the nitric oxide generator, S-nitrosoglutathione (GSNO) reversibly inhibited oxygen utilisation with all substrates tested. The visible absorption spectra of the inhibited mitochondria showed that cytochromes c+c1, b and a+a3 were reduced, indicating a block at the d...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(94)00424-2

    authors: Cleeter MW,Cooper JM,Darley-Usmar VM,Moncada S,Schapira AH

    更新日期:1994-05-23 00:00:00

  • Persistent TNF-alpha exposure impairs store operated calcium influx in CD4+ T lymphocytes.

    abstract::Persistent tumour necrosis factor alpha (TNF-alpha) exposure uncouples proximal T-cell receptor (TCR)-signalling events. Here, we demonstrate that chronic TNF-alpha exposure also attenuates signalling distal to the TCR, by specifically inhibiting Ca2+ influx evoked by thapsigargin in CD4+ T-cells. Mitogen-induced Ca2+...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2005.01.051

    authors: Church LD,Goodall JE,Rider DA,Bacon PA,Young SP

    更新日期:2005-02-28 00:00:00

  • Structure of membrane-bound human factor Va.

    abstract::Coagulation factor Va is an essential cofactor which combines with the serine protease factor Xa on a phospholipid surface to form the prothrombinase complex. In the present study, the structure of factor Va interacting with lipid surfaces containing phosphatidylserine was studied by electron microscopy. Two-dimension...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(94)00881-7

    authors: Stoylova S,Mann KG,Brisson A

    更新日期:1994-09-12 00:00:00

  • Cold-induced mitochondrial uncoupling and expression of chicken UCP and ANT mRNA in chicken skeletal muscle.

    abstract::Although bird species studied thus far have no distinct brown adipose tissue (BAT) or a related thermogenic tissue, there is now strong evidence that non-shivering mechanisms in birds may play an important role during cold exposure. Recently, increased expression of the duckling homolog of the avian uncoupling protein...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(02)03395-1

    authors: Toyomizu M,Ueda M,Sato S,Seki Y,Sato K,Akiba Y

    更新日期:2002-10-09 00:00:00

  • Contribution of IL-12R mediated feedback loop to Th1 cell differentiation.

    abstract::T helper 1 (Th1) cell fate is induced by overlapping signaling pathways, whose kinetic principles and regulatory motifs are largely unknown. We identified a simple positive feedback loop in the STAT4 signaling pathway, whereby activation by IL-12 leads to the increased expression in IL-12 receptor. A computational ana...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2007.10.007

    authors: Becskei A,Grusby MJ

    更新日期:2007-11-13 00:00:00

  • A protein produced by a monocytic human cell line can induce apoptosis on tumor cells.

    abstract::A serum-free medium conditioned by U937, a human cell line of monocyte/macrophage origin, was found capable of inducing apoptosis on exponentially growing U937 cells themselves (autocrine suicide). The apoptosis-inducing agent is a macromolecule and possibly a protein (SKT factor), with a relative molecular mass in th...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(94)00287-8

    authors: Ghibelli L,Coppola S,Nosseri C,Bergamini A,Beninati S

    更新日期:1994-05-09 00:00:00

  • Cigarette smoking products suppress anti-viral effects of Type I interferon via phosphorylation-dependent downregulation of its receptor.

    abstract::While negative effect of smoking on the resistance to viral infections was known, the underlying mechanisms remained unclear. Here we report that products of cigarette smoking compromise the cellular anti-viral defenses by inhibiting the signaling induced by Type I interferon (IFN). Cigarette smoking condensate (but n...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2008.08.013

    authors: HuangFu WC,Liu J,Harty RN,Fuchs SY

    更新日期:2008-09-22 00:00:00

  • Site-directed mutagenesis of alanine-382 of human antithrombin III.

    abstract::Antithrombin III Hamilton is a structural variant of antithrombin III (AT-III) with normal heparin affinity but impaired serine protease inhibitory activity. The molecular defect of AT-III-Hamilton is a substitution of threonine for alanine at amino acid residue 382. Recently it has been shown that both plasma-derived...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(91)80305-m

    authors: Austin RC,Rachubinski RA,Blajchman MA

    更新日期:1991-03-25 00:00:00

  • Poly(A) polymerase (PAP) diversity in gene expression--star-PAP vs canonical PAP.

    abstract::Almost all eukaryotic mRNAs acquire a poly(A) tail at the 3'-end by a concerted RNA processing event: cleavage and polyadenylation. The canonical PAP, PAPα, was considered the only nuclear PAP involved in general polyadenylation of mRNAs. A phosphoinositide-modulated nuclear PAP, Star-PAP, was then reported to regulat...

    journal_title:FEBS letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.febslet.2014.05.029

    authors: Laishram RS

    更新日期:2014-06-27 00:00:00

  • The BAH (bromo-adjacent homology) domain: a link between DNA methylation, replication and transcriptional regulation.

    abstract::Using sensitive methods of sequence analysis including hydrophobic cluster analysis, we report here a hitherto undescribed family of modules, the BAH (bromo-adjacent homology) family, which includes proteins such as eukaryotic DNA (cytosine-5) methyltransferases, the origin recognition complex 1 (Orc1) proteins, as we...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(99)00132-5

    authors: Callebaut I,Courvalin JC,Mornon JP

    更新日期:1999-03-05 00:00:00

  • Occurrence of sialidase activity in two distinct and highly homogeneous populations of lysosomes prepared from the brain of developing mouse.

    abstract::Light and heavy lysosomes of mouse forebrain were separated from each other by centrifugation on a Percoll gradient. Light lysosomes were then freed from mitochondria and membranes by sucrose density gradient centrifugation and further purified by floatation-centrifugation on a sucrose gradient. The final preparations...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(91)80485-l

    authors: Fiorilli A,Siniscalco C,Chiarini A,Di Francesco L,Venerando B,Tettamanti G

    更新日期:1991-05-06 00:00:00

  • A new intrinsic fluorescent probe for proteins. Biosynthetic incorporation of 5-hydroxytryptophan into oncomodulin.

    abstract::The tryptophan analog, 5-hydroxytryptophan (5HW), has a significant absorbance between 310-320 nm, which allows it to act as an exclusive fluorescence probe in protein mixtures containing a large number of tryptophan residues. Here for the first time a method is reported for the biosynthetic incorporation of 5HW into ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(92)81346-n

    authors: Hogue CW,Rasquinha I,Szabo AG,MacManus JP

    更新日期:1992-10-05 00:00:00

  • Altered lysosome distribution is an early neuropathological event in neurological forms of Gaucher disease.

    abstract::In the lysosomal storage disorder Gaucher disease (GD), glucosylceramide (GlcCer) accumulates due to the defective activity of glucocerebrosidase. A subset of GD patients develops neuropathology. We now show mislocalization of Limp2-positive puncta and a large reduction in the number of Lamp1-positive puncta, which ar...

    journal_title:FEBS letters

    pub_type: 信件

    doi:10.1002/1873-3468.12591

    authors: Zigdon H,Meshcheriakova A,Farfel-Becker T,Volpert G,Sabanay H,Futerman AH

    更新日期:2017-03-01 00:00:00

  • Expression of biologically active hormone-sensitive lipase in mammalian (COS) cells.

    abstract::cDNAs encoding rat adipose tissue hormone-sensitive lipase were expressed in COS cells, under the control of the SV40 promoter to half the level in rat adipocytes, the richest native source of the enzyme. A cDNA lacking most of the long 5'-untranslated region of the full-length rat hormone-sensitive lipase cDNA was, w...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(91)80744-n

    authors: Holm C,Davis RC,Fredrikson G,Belfrage P,Schotz MC

    更新日期:1991-07-08 00:00:00

  • Monovalent carboxylic ionophores inhibit transport of carbamoyl-phosphate synthetase I into mitochondria in Reuber hepatoma H-35 cells and cause accumulation of enzyme precursor.

    abstract::Transport of the precursor for carbamoyl-phosphate synthetase I into mitochondria in Reuber hepatoma H-35 cells was inhibited by adding monensin or nigericin to the culture medium at a concentration of 0.5 microM, and the enzyme precursor accumulated, mainly in the cytosolic fraction. Accumulated precursor was degrade...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(84)80029-0

    authors: Kitagawa Y,Murakami A,Sugimoto E

    更新日期:1984-01-02 00:00:00

  • Overexpression of OsMYB1R1-VP64 fusion protein increases grain yield in rice by delaying flowering time.

    abstract::VP64 is widely used as a transcriptional activator to investigate the biological function of genes, but its potential for application in genetic improvement of crops has not been fully investigated. Here, we characterized an OsMYB1R1-VP64 fusion protein that enhanced the grain yield of rice cultivar 'Kita-ake' by 35%....

    journal_title:FEBS letters

    pub_type: 信件

    doi:10.1002/1873-3468.12374

    authors: Wang J,Wu F,Zhu S,Xu Y,Cheng Z,Wang J,Li C,Sheng P,Zhang H,Cai M,Guo X,Zhang X,Wang C,Wan J

    更新日期:2016-10-01 00:00:00

  • Cloning and expression of the epsilon 4 subunit of the NMDA receptor channel.

    abstract::The primary structure of a novel subunit of the mouse NMDA (N-methyl-D-aspartate) receptor channel, designated epsilon 4, has been revealed by cloning and sequencing the cDNA. The epsilon 4 subunit shares high amino acid sequence identity with the epsilon 1, epsilon 2 and epsilon 3 subunits of the mouse NMDA receptor ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(92)81178-o

    authors: Ikeda K,Nagasawa M,Mori H,Araki K,Sakimura K,Watanabe M,Inoue Y,Mishina M

    更新日期:1992-11-16 00:00:00

  • Biochemical evidence for the interaction of regulatory subunit of cAMP-dependent protein kinase with IDA (Inter-DFG-APE) region of catalytic subunit.

    abstract::To explore the structural basis required for the holoenzyme formation of cAMP-dependent protein kinase, we have prepared rabbit anti-peptide antibodies that can block the holoenzyme formation without affecting the catalytic activity of the enzyme. The antibodies were raised against a specific site in the catalytic (C)...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(96)00302-x

    authors: Sahara S,Sato K,Kaise H,Mori K,Sato A,Aoto M,Tokmakov AA,Fukami Y

    更新日期:1996-04-15 00:00:00

  • Single-chain precursor of renal gamma-glutamyl transpeptidase.

    abstract::The two subunits of gamma-glutamyl transpeptidase (EC 2.3.2.2) are derived from a single-chain glycosylated precursor. A small fraction of the propeptide survives proteolytic processing in the rat kidney and has been purified by an immunoaffinity technique. The propeptide contains determinants for both the subunits an...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(86)80046-1

    authors: Tate SS

    更新日期:1986-01-01 00:00:00

  • Highly selective affinity labeling of the primer-binding site of E. coli DNA polymerase I.

    abstract::Highly selective affinity labeling of the primer site of E. coli DNA polymerase I was performed with the 5'-reactive derivatives of oligothymidylate in the presence of poly(dA) template. Subtilysine cleavage proved that the site of affinity modification belonged to the 'Klenow' part of DNA polymerase I. If taken separ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(90)80478-2

    authors: Mitina RL,Mustaev AA,Zaychikov EF,Khomov VV,Lavrik OI

    更新日期:1990-10-15 00:00:00

  • Misacylation of pyrrolysine tRNA in vitro and in vivo.

    abstract::Methanosarcina barkeri inserts pyrrolysine (Pyl) at an in-frame UAG codon in its monomethylamine methyltransferase gene. Pyrrolysyl-tRNA synthetase acylates Pyl onto tRNAPyl, the amber suppressor pyrrolysine Pyl tRNA. Here we show that M. barkeri Fusaro tRNAPyl can be misacylated with serine by the M. barkeri bacteria...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2008.08.027

    authors: Gundllapalli S,Ambrogelly A,Umehara T,Li D,Polycarpo C,Söll D

    更新日期:2008-10-15 00:00:00

  • Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation.

    abstract::NELL1 is an extracellular protein inducing osteogenic differentiation and bone formation of osteoblastic cells. To elucidate the intracellular signaling cascade evoked by NELL1, we have shown that NELL1 protein transiently activates the MAPK signaling cascade, induces the phosphorylation of Runx2, and promotes the rap...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2007.12.006

    authors: Bokui N,Otani T,Igarashi K,Kaku J,Oda M,Nagaoka T,Seno M,Tatematsu K,Okajima T,Matsuzaki T,Ting K,Tanizawa K,Kuroda S

    更新日期:2008-01-23 00:00:00

  • A specific immunological probe for the major myelin proteolipid. Confirmation of a deletion in DM-20.

    abstract::Major myelin proteolipid (MMPL, also called PLP) and DM-20 are the two major intrinsic membrane proteins of CNS myelin. A specific immunological probe was obtained for MMPL by raising antibodies against the synthetic tridecapeptide 117-129 of MMPL. Antibodies against this peptide reacted with the MMPL but did not cros...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(86)80412-4

    authors: Trifilieff E,Luu B,Nussbaum JL,Roussel G,Espinosa de los Monteros A,Sabatier JM,Van Rietschoten J

    更新日期:1986-03-31 00:00:00

  • Geometry of binding of the N alpha-tosylated piperidides of m-amidino-, p-amidino- and p-guanidino phenylalanine to thrombin and trypsin. X-ray crystal structures of their trypsin complexes and modeling of their thrombin complexes.

    abstract::The X-ray crystal structures of the complexes formed with bovine trypsin and the N alpha-tosylated piperidides of m-amidino-, p-amidino- and p-guanidino-D,L-phenylalanine (3-TAPAP, 4-TAPAP and 4-TGPAP) were determined with data to 1.8 A resolution. The L-stereoisomer of 3-TAPAP binds as a compact entity into the activ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(91)80033-y

    authors: Turk D,Stürzebecher J,Bode W

    更新日期:1991-08-05 00:00:00

  • Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs.

    abstract::The crystal structure of human immunodeficiency virus type 1 (HIV-1) protease mutant G48H with peptidic inhibitor U-89360E is described. Comparison with wild-type protease-inhibitor complex shows that mutation of flap residue 48 to histidine allows stabilizing van der Waals contacts between the side chains of His48 an...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(97)01477-4

    authors: Hong L,Zhang XJ,Foundling S,Hartsuck JA,Tang J

    更新日期:1997-12-22 00:00:00

  • Characterization of yeast fructose-2,6-bisphosphate 6-phosphatase.

    abstract::To obtain information on the biological significance of yeast fructose-2,6-bisphosphate 6-phosphatase, kinetic data of the purified enzyme [(1987) Eur. J. Biochem. 164, 27-30] have been measured. Maximal activity was found between pH 6 and 7, the apparent Michaelis constant with fructose 2,6-bisphosphate was 7.2 micro...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(88)80547-7

    authors: Plankert U,Purwin C,Holzer H

    更新日期:1988-10-24 00:00:00

  • Evolution of dnaQ, the gene encoding the editing 3' to 5' exonuclease subunit of DNA polymerase III holoenzyme in Gram-negative bacteria.

    abstract::The nucleotide sequences of the dnaQ genes from Salmonella typhimurium and Buchnera aphidicola, encoding the epsilon-subunit of the DNA polymerase III holoenzyme, have been determined. The Salmonella typhimurium dnaQ protein consists of 243 amino acid residues with a calculated molecular weight of 27224. The Buchnera ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(96)01361-0

    authors: Huang Y,Braithwaite DK,Ito J

    更新日期:1997-01-02 00:00:00

  • The tail nick augments Aeromonas sobria serine protease (ASP) activity in plasma through retarding inhibition by α2-macroglobulin.

    abstract::ASP is a serine protease secreted by Aeromonas sobria, a sepsis-causing bacterium, and induces sepsis-mimicking disorders through plasma protein cleavage. The pathogen also secretes nASP that has a nick in the carboxy-terminal region. Compared with single-chain ASP (sASP), nASP had near-equivalent activity for small p...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2012.08.004

    authors: Murakami Y,Wada Y,Kobayashi H,Hasegawa M,Okamoto K,Eto M,Imamura T

    更新日期:2012-10-19 00:00:00

  • The caffeine-sensitive Ca2+ store in bovine adrenal chromaffin cells; an examination of its role in triggering secretion and Ca2+ homeostasis.

    abstract::The effect of caffeine on catecholamine secretion and intracellular free Ca2+ concentration [( Ca2+]i) in bovine adrenal chromaffin cells was examined using single fura-2-loaded cells and cell populations. In cell populations caffeine elicited a large (approximately 200 nM) transient rise in [Ca2+]i that was independe...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(90)81514-o

    authors: Cheek TR,O'Sullivan AJ,Moreton RB,Berridge MJ,Burgoyne RD

    更新日期:1990-06-18 00:00:00