AcpM, the meromycolate extension acyl carrier protein of Mycobacterium tuberculosis, is activated by the 4'-phosphopantetheinyl transferase PptT, a potential target of the multistep mycolic acid biosynthesis.


:Modification of acyl carrier proteins (ACP) or domains by the covalent binding of a 4'-phosphopantetheine (4'-PP) moiety is a fundamental condition for activation of fatty acid synthases (FASes) and polyketide synthases (PKSes). Binding of 4'-PP is mediated by 4' phosphopantetheinyl transfersases (PPTases). Mycobacterium tuberculosis (Mtb) possesses two essential PPTases: acyl carrier protein synthase (Mtb AcpS), which activates the multidomain fatty acid synthase I (FAS I), and Mtb PptT, an Sfp-type broad spectrum PPTase that activates PKSes. To date, it has not been determined which of the two Mtb PPTases, AcpS or PptT, activates the meromycolate extension ACP, Mtb AcpM, en route to the production of mycolic acids, the main components of the mycobacterial cell wall. In this study, we tested the enzymatic activation of a highly purified Mtb apo-AcpM to Mtb holo-AcpM by either Mtb PptT or Mtb AcpS. By using SDS-PAGE band shift assay and mass spectrometry analysis, we found that Mtb PptT is the PPTase that activates Mtb AcpM. We measured the catalytic activity of Mtb PptT toward CoA, using an activation assay of a blue pigment synthase, BpsA (a nonribosomal peptide synthase, NRPS). BpsA activation by Mtb PptT was inhibited by Mtb apo-AcpM through competition for CoA, in accord with Mtb AcpM activation. A structural model of the putative interaction between Mtb PptT and Mtb AcpM suggests that both hydrophobic and electrostatic interactions stabilize this complex. To conclude, activation of Mtb AcpM by Mtb PptT reveals a potential target of the multistep mycolic acid biosynthesis.






Zimhony O,Schwarz A,Raitses-Gurevich M,Peleg Y,Dym O,Albeck S,Burstein Y,Shakked Z




Has Abstract


2015-04-14 00:00:00












  • The red blood cell glucose transporter presents multiple, nucleotide-sensitive sugar exit sites.

    abstract::At any instant, the human erythrocyte sugar transporter presents at least one sugar export site but multiple sugar import sites. The present study asks whether the transporter also presents more than one sugar exit site. We approached this question by analysis of binding of [3H]cytochalasin B (an export conformer liga...


    pub_type: 杂志文章


    authors: Cloherty EK,Levine KB,Carruthers A

    更新日期:2001-12-25 00:00:00

  • NMR structure of the extended Myb cognate sequence and modeling studies on specific DNA-Myb complexes.

    abstract::The recognition sequence of the Myb protein has been recently described to be pyAACKGHH (where py = T/C, K = G/T, and H = A/C/T), modifying the earlier identification as pyAACKG [Ording, E., et al. (1994) Eur. J. Biochem. 222, 113-120]. We had earlier determined the solution structure of the minimal cognate sequence T...


    pub_type: 杂志文章


    authors: Radha PK,Patel PK,Hosur RV

    更新日期:1998-07-14 00:00:00

  • Crystal structure of arginase from Plasmodium falciparum and implications for L-arginine depletion in malarial infection .

    abstract::The 2.15 A resolution crystal structure of arginase from Plasmodium falciparum, the parasite that causes cerebral malaria, is reported in complex with the boronic acid inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) (K(d) = 11 microM). This is the first crystal structure of a parasitic arginase. Various protein const...


    pub_type: 杂志文章


    authors: Dowling DP,Ilies M,Olszewski KL,Portugal S,Mota MM,Llinás M,Christianson DW

    更新日期:2010-07-06 00:00:00

  • Subgel phases of n-saturated diacylphosphatidylcholines: a Fourier-transform infrared spectroscopic study.

    abstract::The subgel phases of a homologous series of saturated straight-chain diacylphosphatidylcholines with hydrocarbon chains consisting of 10-18 carbon atoms were studied by Fourier-transform infrared spectroscopy. All of these lipids initially form a subgel phase which is spectroscopically similar to that obtained when fu...


    pub_type: 杂志文章


    authors: Lewis RN,McElhaney RN

    更新日期:1990-08-28 00:00:00

  • Integrated function of a kinetic proofreading mechanism: steady-state analysis testing internal consistency of data obtained in vivo and in vitro and predicting parameter values.

    abstract::Experimental measurements of the kinetic mechanism involving isoleucyl-tRNA synthetase proofreading valyl-tRNAIle in Escherichia coli have been incorporated into the conventional Michaelis-Menten model for this system. The model was subjected to a detailed mathematical analysis in the steady state. The results of this...


    pub_type: 杂志文章


    authors: Okamoto M,Savageau MA

    更新日期:1984-04-10 00:00:00

  • Investigating the structural dynamics of α-1,4-galactosyltransferase C from Neisseria meningitidis by nuclear magnetic resonance spectroscopy.

    abstract::Neisseria meningitidis α-1,4-galactosyltransferase C (LgtC) is responsible for the transfer of α-galactose from donor UDP-galactose to the lipooligosaccharide terminal acceptor lactose. Crystal structures of its substrate analogue complexes have provided key insights into the galactosyl transfer mechanism, including a...


    pub_type: 杂志文章


    authors: Chan PH,Cheung AH,Okon M,Chen HM,Withers SG,McIntosh LP

    更新日期:2013-01-15 00:00:00

  • Phosphatidyl-Tris rather than N-acylphosphatidylserine is synthesized by Rhodopseudomonas sphaeroides grown in Tris-containing media.

    abstract::We have synthesized 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho(N-oleoyl)serine (N-acyl-PS) and 1,2-dioleoyl-sn-glycero-3-phospho-Tris (phosphatidyl-Tris) and have characterized both phospholipids by their chemical and chromatographic properties, as well as by their IR, 13C NMR, and 1H NMR spectra. Comparison of these d...


    pub_type: 杂志文章


    authors: Schmid PC,Kumar VV,Weis BK,Schmid HH

    更新日期:1991-02-19 00:00:00

  • Nuclear Magnetic Resonance Solution Structure of DNA Featuring Clustered 2'-Deoxyribonolactone and 8-Oxoguanine Lesions.

    abstract::Ionizing radiation, free radicals, and reactive oxygen species produce hundreds of different DNA lesions. Clustered lesions are typical for ionizing radiation. They compromise the efficiency of the base excision repair (BER) pathway, and as a consequence, they are much more toxic and mutagenic than isolated lesions. D...


    pub_type: 杂志文章


    authors: Zálešák J,Constant JF,Jourdan M

    更新日期:2016-07-19 00:00:00

  • Structural dynamics in the plastocyanin-photosystem 1 electron-transfer complex as revealed by mutant studies.

    abstract::A series of plastocyanin mutants have been constructed by site-directed mutagenesis and expressed in Escherichia coli to elucidate the interaction between plastocyanin and photosystem 1 in the photosynthetic electron-transfer chain. Leu-12 has been replaced with alanine, asparagine, glutamate, and lysine, while Tyr-83...


    pub_type: 杂志文章


    authors: Sigfridsson K,Young S,Hansson O

    更新日期:1996-01-30 00:00:00

  • NMR solution structure of the C-terminal fragment 255-316 of thermolysin: a dimer formed by subunits having the native structure.

    abstract::The solution structure of the C-terminal fragment 255-316 of thermolysin has been determined by two-dimensional proton NMR methods. For this disulfide-free fragment there was a previous proposal according to which it would fold into a stable helical structure forming a dimer at concentrations above 0.06 mM. A complete...


    pub_type: 杂志文章


    authors: Rico M,Jiménez MA,González C,De Filippis V,Fontana A

    更新日期:1994-12-13 00:00:00

  • Conformation and stability of the constant fragment of the immunoglobulin light chain containing an intramolecular mercury bridge.

    abstract::The constant fragment of the immunoglobulin light chain in which the intramolecular disulfide bond is reduced (reduced CL fragment) assumes a conformation very similar to that of the intact CL fragment and contains two sulfhydryl groups buried in the interior of the molecule [Goto, Y., & Hamaguchi, K. (1979) J. Bioche...


    pub_type: 杂志文章


    authors: Goto Y,Hamaguchi K

    更新日期:1986-05-20 00:00:00

  • Involvement of insulin-like growth factor type 1 receptor and protein kinase Cdelta in bis(maltolato)oxovanadium(IV)-induced phosphorylation of protein kinase B in HepG2 cells.

    abstract::Vanadium(IV) oxo-bis(maltolato) (BMOV), an organovanadium compound, is a potent insulinomimetic agent and improves glucose homeostasis in various models of diabetes. We have shown previously that BMOV stimulates the phosphorylation of PKB which may contribute as one of the mechanisms for the insulinomimetic effect of ...


    pub_type: 杂志文章


    authors: Mehdi MZ,Vardatsikos G,Pandey SK,Srivastava AK

    更新日期:2006-09-26 00:00:00

  • Probing adenine rings and backbone linkages using base specific isotope-edited Raman spectroscopy: application to group II intron ribozyme domain V.

    abstract::Raman difference spectroscopy is used to probe the properties of a 36-nt RNA molecule, "D5", which lies at the heart of the catalytic apparatus in group II introns. For D5 that has all of its adenine residues labeled with (13)C and (15)N and utilizing Raman difference spectroscopy, we identify the conformationally sen...


    pub_type: 杂志文章


    authors: Chen Y,Eldho NV,Dayie TK,Carey PR

    更新日期:2010-04-27 00:00:00

  • Structural requirements for formyl homooligopeptide chemoattractants.

    abstract::Using solution peptide synthesis, we have made three series of N alpha-formylated homooligopeptides, from the dipeptide to the heptapeptide, derived from L-methionine, L-norleucine, and S-methyl-L-cysteine and related to the chemotactic peptide N alpha-formylmethionylleucylphenylalanine. Compounds were prepared to det...


    pub_type: 杂志文章


    authors: Toniolo C,Bonora GM,Showell H,Freer RJ,Becker EL

    更新日期:1984-02-14 00:00:00

  • Examination of sodium/glucose cotransport by using a visible glucose analogue.

    abstract::The glucose derivative, 2,2,6,6-tetramethylpiperidine-1-oxylglucose (TEMPO-glucose) was synthesized and examined for its ability to substitute for glucose as a substrate for the intestinal brush border membrane Na+/glucose cotransporter. TEMPO-glucose inhibited Na(+)-dependent phlorizin binding with an apparent KI of ...


    pub_type: 杂志文章


    authors: Peerce BE

    更新日期:1991-04-30 00:00:00

  • Inactivation of human lung tryptase: evidence for a re-activatable tetrameric intermediate and active monomers.

    abstract::Human lung tryptase (HLT), a trypsin-like serine proteinase stored as an active enzyme in association with heparin in mast cell granules, is released into the extracellular environment when mast cells are activated. Tryptases are unusual in that they form tetramers and bind heparin. As there are no known endogenous tr...


    pub_type: 杂志文章


    authors: Addington AK,Johnson DA

    更新日期:1996-10-22 00:00:00

  • Side-chain dynamics of two aromatic amino acids in pancreatic phospholipase A2 as studied by deuterium nuclear magnetic resonance.

    abstract::The flexibility of individual amino acid side chains of pancreatic phospholipase A2 in aqueous and micellar solutions was studied with deuterium nuclear magnetic resonance (2H NMR). Bovine pancreatic phospholipase A2 was selectively deuterated at the aromatic ring systems of Trp-3 and Phe-5 and porcine pancreatic phos...


    pub_type: 杂志文章


    authors: Allegrini PR,van Scharrenburg GJ,Slotboom AJ,de Haas GH,Seelig J

    更新日期:1985-06-18 00:00:00

  • Synergistic interactions of multiple mutations on catalysis during the hydroxylation reaction of p-hydroxybenzoate hydroxylase: studies of the Lys297Met, Asn300Asp, and Tyr385Phe mutants reconstituted with 8-Cl-flavin.

    abstract::The oxygen transfer to p-hydroxybenzoate catalyzed by p-hydroxybenzoate hydroxylase (PHBH) has been shown to occur via a C4a-hydroperoxide of the flavin. Two factors are likely to be important in facilitating the transfer of oxygen from the C4a-hydroperoxide to the substrate. (a) The positive electrostatic potential o...


    pub_type: 杂志文章


    authors: Ortiz-Maldonado M,Aeschliman SM,Ballou DP,Massey V

    更新日期:2001-07-31 00:00:00

  • Ligand stabilization of the beta 2 adrenergic receptor: effect of DTT on receptor conformation monitored by circular dichroism and fluorescence spectroscopy.

    abstract::Treatment of the beta 2 adrenergic receptor with the reducing agent dithiothreitol (DTT) is known to abolish ligand binding to the receptor. Interestingly, the loss of binding can be prevented by preoccupation of the receptor with ligand. It is unclear, however, whether the ligand blocks access of DTT to the receptor,...


    pub_type: 杂志文章


    authors: Lin S,Gether U,Kobilka BK

    更新日期:1996-11-19 00:00:00

  • Heme and cysteine microenvironments of tuna apomyoglobin. Evidence of two independent unfolding regions.

    abstract::The heme and cysteine microenvironments of bluefin tuna apomyoglobin have been investigated by examining the fluorescence properties of two extrinsic chromophores, i.e., ANS and 1,5-AEDANS. 1,5-AEDANS was covalently bound to the single cysteine residue found in the primary structure of tuna apomyoglobin. Recombination...


    pub_type: 杂志文章


    authors: Colonna G,Balestrieri C,Bismuto E,Servillo L,Irace G

    更新日期:1982-01-19 00:00:00

  • Characterization of prostate-specific antigen proteolytic activity on its major physiological substrate, the sperm motility inhibitor precursor/semenogelin I.

    abstract::The protease prostate-specific antigen (PSA) is a marker widely used clinically for monitoring prostatic malignancies. Under normal conditions, this enzyme is mainly involved in the post ejaculation degradation of the major human seminal protein, the seminal plasma motility inhibitor precursor/semenogelin I (SPMIP/SgI...


    pub_type: 杂志文章


    authors: Robert M,Gibbs BF,Jacobson E,Gagnon C

    更新日期:1997-04-01 00:00:00

  • Direct measurement of the interactions of glycosaminoglycans and a heparin decasaccharide with the malaria circumsporozoite protein.

    abstract::Circumsporozoite (CS) protein is a predominant surface antigen of malaria sporozoites, the infective form of the parasite, and has been used for making anti-malaria vaccines. For the first time we have examined the interaction of CS protein with various glycosaminoglycans in real time using surface plasmon resonance (...


    pub_type: 杂志文章


    authors: Rathore D,McCutchan TF,Garboczi DN,Toida T,Hernáiz MJ,LeBrun LA,Lang SC,Linhardt RJ

    更新日期:2001-09-25 00:00:00

  • Stereochemistry of phospho group transfer catalyzed by a mutant alkaline phosphatase.

    abstract::The stereochemical course of the phospho group transfer catalyzed by mutant (S102C) alkaline phosphatase from Escherichia coli was investigated by using 31P nuclear magnetic resonance spectroscopy. Transphosphorylation from 4-nitrophenyl (Rp)-[16O, 17O, 18O]phosphate to (S)-propane-1,2-diol occurs with overall retenti...


    pub_type: 杂志文章


    authors: Butler-Ransohoff JE,Kendall DA,Freeman S,Knowles JR,Kaiser ET

    更新日期:1988-06-28 00:00:00

  • Mapping of DNA alkylation sites induced by adozelesin and bizelesin in human cells by ligation-mediated polymerase chain reaction.

    abstract::In this study, we have mapped the intracellular alkylation sites of adozelesin and bizelesin, two potent analogs of CC-1065, in individual genes at the single-nucleotide level. Human colon carcinoma cells were treated with adozelesin and bizelesin, and the position of adducts were mapped within the PGK-1 and p53 genes...


    pub_type: 杂志文章


    authors: Lee CS,Pfeifer GP,Gibson NW

    更新日期:1994-05-17 00:00:00

  • Ia-associated invariant chain is fatty acylated before addition of sialic acid.

    abstract::The murine invariant chain (Ii) was found to incorporate radioactive palmitic acid. This binding of fatty acid inhibits the formation of interchain S-S bonds, probably because the cysteine residue in the transmembrane region of the Ii chain is palmitylated. The inhibition of fatty acylation by cerulenin blocks further...


    pub_type: 杂志文章


    authors: Koch N,Hämmerling GJ

    更新日期:1985-10-22 00:00:00

  • Direct electrochemistry of protein-protein complexes involving cytochrome c, cytochrome b5, and plastocyanin.

    abstract::The direct electrochemistry of the cytochrome c/cytochrome b5 and cytochrome c/plastocyanin complexes has been investigated at edge-plane graphite and modified gold electrode surfaces, which are selective for one of the two components of the complex. Electrochemical response of one protein at an otherwise electrostati...


    pub_type: 杂志文章


    authors: Bagby S,Barker PD,Guo LH,Hill HA

    更新日期:1990-04-03 00:00:00

  • Purification and characterization of selenomethionyl thymidylate synthase from Escherichia coli: comparison with the wild-type enzyme.

    abstract::Replacement of methionine (Met) residues by selenomethionine (SeMet) was recently shown to facilitate the crystallographic analysis of protein structure through the application of multi-wavelength anomalous diffraction techniques [Yang et al. (1990) Science (Washington, D.C.) 249, 1398-1405]. The availability of SeMet...


    pub_type: 杂志文章


    authors: Boles JO,Cisneros RJ,Weir MS,Odom JD,Villafranca JE,Dunlap RB

    更新日期:1991-11-19 00:00:00

  • A fluorescence anisotropy study of DNA binding by HPV-11 E2C protein: a hierarchy of E2-binding sites.

    abstract::Association of the human papillomavirus (HPV) E2 protein with its palindromic DNA-binding site is a necessary step for transcriptional trans-activation. To study the interaction between DNA and E2, the carboxyl-terminal domain of HPV-11 E2 protein (E2C) was expressed in Escherichia coli and purified to homogeneity. Th...


    pub_type: 杂志文章


    authors: Alexander KA,Phelps WC

    更新日期:1996-07-30 00:00:00

  • A distinctive RNA fold: the solution structure of an analogue of the yeast tRNAPhe T Psi C domain.

    abstract::The structure of an analogue of the yeast tRNAPhe T Psi C stem-loop has been determined by NMR spectroscopy and restrained molecular dynamics. The molecule contained the highly conserved modification ribothymidine at its naturally occurring position. The ribothymidine-modified T Psi C stem-loop is the product of the m...


    pub_type: 杂志文章


    authors: Koshlap KM,Guenther R,Sochacka E,Malkiewicz A,Agris PF

    更新日期:1999-07-06 00:00:00

  • Structure of alpha-glycerophosphate oxidase from Streptococcus sp.: a template for the mitochondrial alpha-glycerophosphate dehydrogenase.

    abstract::The FAD-dependent alpha-glycerophosphate oxidase (GlpO) from Enterococcus casseliflavus and Streptococcus sp. was originally studied as a soluble flavoprotein oxidase; surprisingly, the GlpO sequence is 30-43% identical to those of the alpha-glycerophosphate dehydrogenases (GlpDs) from mitochondrial and bacterial sour...


    pub_type: 杂志文章


    authors: Colussi T,Parsonage D,Boles W,Matsuoka T,Mallett TC,Karplus PA,Claiborne A

    更新日期:2008-01-22 00:00:00