Structural basis for substrate binding and the catalytic mechanism of type III pantothenate kinase.


:Pantothenate kinase (PanK) catalyzes the first step of the universal five-step coenzyme A (CoA) biosynthetic pathway. The recently characterized type III PanK (PanK-III, encoded by the coaX gene) is distinct in sequence, structure and enzymatic properties from both the long-known bacterial type I PanK (PanK-I, exemplified by the Escherichia coli CoaA protein) and the predominantly eukaryotic type II PanK (PanK-II). PanK-III enzymes have an unusually high Km for ATP, are resistant to feedback inhibition by CoA, and are unable to utilize the N-alkylpantothenamide family of pantothenate analogues as alternative substrates, thus making type III PanK ineffective in generating CoA analogues as antimetabolites in vivo. Previously, we reported the crystal structure of the PanK-III from Thermotoga maritima and identified it as a member of the "acetate and sugar kinase/heat shock protein 70/actin" (ASKHA) superfamily. Here we report the crystal structures of the same PanK-III in complex with one of its substrates (pantothenate), its product (phosphopantothenate) as well as a ternary complex structure of PanK-III with pantothenate and ADP. These results are combined with isothermal titration calorimetry experiments to present a detailed structural and thermodynamic characterization of the interactions between PanK-III and its substrates ATP and pantothenate. Comparison of substrate binding and catalytic sites of PanK-III with that of eukaryotic PanK-II revealed drastic differences in the binding modes for both ATP and pantothenate substrates, and suggests that these differences may be exploited in the development of new inhibitors specifically targeting PanK-III.






Yang K,Strauss E,Huerta C,Zhang H




Has Abstract


2008-02-05 00:00:00












  • Assignment of spectral substructures to pigment-binding sites in higher plant light-harvesting complex LHC-II.

    abstract::The trimeric main light-harvesting complex (LHC-II) is the only antenna complex of higher plants of which a high-resolution 3D structure has been obtained (Kühlbrandt, W., Wang, D., and Fujiyoshi, Y. (1994) Nature 367, 614-621) and which can be refolded in vitro from its components. Four different recombinant forms of...


    pub_type: 杂志文章


    authors: Rogl H,Schödel R,Lokstein H,Kühlbrandt W,Schubert A

    更新日期:2002-02-19 00:00:00

  • Characterization of a soluble adrenal phosphatidylinositol 4-kinase reveals wortmannin sensitivity of type III phosphatidylinositol kinases.

    abstract::Phosphorylation of phosphatidylinositol (PtdIns) by PtdIns 4-kinases is the first step in the synthesis of polyphosphoinositides, the lipid precursors of intracellular signaling molecules. We have recently identified a cytosolic PtdIns 4-kinase (cPI4K) in the bovine adrenal cortex that is distinguished from previously...


    pub_type: 杂志文章


    authors: Downing GJ,Kim S,Nakanishi S,Catt KJ,Balla T

    更新日期:1996-03-19 00:00:00

  • Effect of temperature on the intrinsic flexibility of DNA and its interaction with architectural proteins.

    abstract::The helical structure of double-stranded DNA is destabilized by increasing temperature. Above a critical temperature (the melting temperature), the two strands in duplex DNA become fully separated. Below this temperature, the structural effects are localized. Using tethered particle motion in a temperature-controlled ...


    pub_type: 杂志文章


    authors: Driessen RP,Sitters G,Laurens N,Moolenaar GF,Wuite GJ,Goosen N,Dame RT

    更新日期:2014-10-21 00:00:00

  • Interfacial catalysis by phospholipase A2: the rate-limiting step for enzymatic turnover.

    abstract::The kinetics of the phospholipase A2-catalyzed hydrolysis of bilayer vesicles and mixed micelles of several oxyglycero and thioglycero analogues of phospholipids have been studied. The results with vesicles show that, depending on the source of the enzyme, the rates of hydrolysis of the oxy-containing long-chain phosp...


    pub_type: 杂志文章


    authors: Jain MK,Yu BZ,Rogers J,Gelb MH,Tsai MD,Hendrickson EK,Hendrickson HS

    更新日期:1992-09-01 00:00:00

  • Chemical modification of tryptophan residues in Escherichia coli succinyl-CoA synthetase. Effect on structure and enzyme activity.

    abstract::Succinyl-CoA synthetase of Escherichia coli is an alpha 2 beta 2 protein containing active sites at the interfaces between alpha- and beta-subunits. The alpha-subunit contains a histidine residue that is phosphorylated during the reaction. The beta-subunit binds coenzyme A and probably succinate [see Nishimura, J. S. ...


    pub_type: 杂志文章


    authors: Ybarra J,Prasad AR,Nishimura JS

    更新日期:1986-11-04 00:00:00

  • DNA-dependent adenosinetriphosphatase B from mouse FM3A cells has DNA helicase activity.

    abstract::We have detected at least four forms of DNA-dependent ATPase in mouse FM3A cell extracts [Tawaragi, Y., Enomoto, T., Watanabe, Y., Hanaoka, F., & Yamada, M. (1984) Biochemistry 23, 529-533]. The purified fraction of one of the four forms, ATPase B, has been shown to have DNA helicase activity by using a DNA substrate ...


    pub_type: 杂志文章


    authors: Seki M,Enomoto T,Hanaoka F,Yamada M

    更新日期:1987-05-19 00:00:00

  • Stereochemistry of the hydrolysis of adenosine 5'-thiophosphate catalyzed by venom 5'-nucleotidase.

    abstract::The stereochemical problem involving a pro-pro-prochiral phosphorus center, the hydrolysis of adenosine 5'-monophosphate to adenosine and inorganic phosphate catalyzed by the venom 5'-nucleotidase, has been studied by use of chiral [16O, 17O, 18O]thiophosphates (Psi). (Rp)- and (Sp)-[alpha-18O1]Adenosine 5'-thiophosph...


    pub_type: 杂志文章


    authors: Tsai MD

    更新日期:1980-11-11 00:00:00

  • Purification and biochemical characterization of tubulin from the budding yeast Saccharomyces cerevisiae.

    abstract::We describe a method for isolating milligram quantities of assembly-competent tubulin from the budding yeast Saccharomyces cerevisiae. The tubulin is > 95% purified and free of contaminating enzyme activities. As a result, it has been possible to determine the yeast tubulin equilibrium-binding constant for Mg-GTP and ...


    pub_type: 杂志文章


    authors: Davis A,Sage CR,Wilson L,Farrell KW

    更新日期:1993-08-31 00:00:00

  • Guanosine tetraphyosphate and its analogues. Chemical synthesis of guanosine 3',5'-dipyrophosphate, deoxyguanosine 3',5'-dipyrophosphate, guanosine 2',5'-bis(methylenediphosphonate), and guanosine 3',5'-bis(methylenediphosphonate).

    abstract::A new procedure for the synthesis of the pyrophosphate bond has been employed in the preparation of nucleoside dipyrophosphates from nucleoside 3',5'-diphosphates. The method makes use of a powerful phosphorylating agent generated in a mixture of cyanoethyl phosphate, dicyclohexylcarbodiimide, and mesitylenesulfonyl c...


    pub_type: 杂志文章


    authors: Bennett GN,Gough GR,Gilham PT

    更新日期:1976-10-19 00:00:00

  • Trifunctional dinuclear platinum complexes as DNA-protein cross-linking agents.

    abstract::The trifunctional dinuclear platinum compounds 1,2/c,c [[cis-PtCl(NH(3))(2)]mu-H(2)N(CH(2))(6)NH(2)[cis-PtCl(2)(NH(3))]](+) and 1,2/t,c [[trans-PtCl(NH(3))(2)]mu-H(2)N(CH(2))(6)NH(2)[cis-PtCl(2)(NH(3))]](+) contain a monofunctional platinum coordination sphere linked to a cis-[PtCl(2)(amine)(2)] moiety. The compounds ...


    pub_type: 杂志文章


    authors: Kloster M,Kostrhunova H,Zaludova R,Malina J,Kasparkova J,Brabec V,Farrell N

    更新日期:2004-06-22 00:00:00

  • Effect of an Imposed Contact on Secondary Structure in the Denatured State of Yeast Iso-1-cytochrome c.

    abstract::There is considerable evidence that long-range interactions stabilize residual protein structure under denaturing conditions. However, evaluation of the effect of a specific contact on structure in the denatured state has been difficult. Iso-1-cytochrome c variants with a Lys54 → His mutation form a particularly stabl...


    pub_type: 杂志文章


    authors: Danielson TA,Stine JM,Dar TA,Briknarova K,Bowler BE

    更新日期:2017-12-26 00:00:00

  • Modulation of GLUT4 and GLUT1 recycling by insulin in rat adipocytes: kinetic analysis based on the involvement of multiple intracellular compartments.

    abstract::The trafficking kinetics of GLUT4 and GLUT1 in rat epididymal adipocytes were analyzed by a four-compartment model based upon steady-state pool sizes of three intracellular fractions and one plasma membrane fraction separated and assessed under both basal and insulin-stimulated states. The steady-state compartment siz...


    pub_type: 杂志文章


    authors: Lee W,Ryu J,Spangler RA,Jung CY

    更新日期:2000-08-08 00:00:00

  • Duplication of a Single Strand in a β-Sheet Can Produce a New Switching Function in a Photosensory Protein.

    abstract::Duplication of a single β-strand that forms part of a β-sheet in photoactive yellow protein (PYP) was found to produce two approximately isoenergetic protein conformations, in which either the first or the second copy of the duplicated β-strand participates in the β-sheet. Whereas one conformation (big-loop) is more s...


    pub_type: 杂志文章


    authors: Kumar A,Nokhrin S,Woloschuk RM,Woolley GA

    更新日期:2018-07-17 00:00:00

  • Conformational heterogeneity at position U37 of an all-RNA hairpin ribozyme with implications for metal binding and the catalytic structure of the S-turn.

    abstract::The hairpin ribozyme is an RNA enzyme that performs site-specific phosphodiester bond cleavage between nucleotides A-1 and G+1 within its cognate substrate. Previous functional studies revealed that the minimal hairpin ribozyme exhibited "gain-of-function" cleavage properties resulting from U39C or U39 to propyl linke...


    pub_type: 杂志文章


    authors: Alam S,Grum-Tokars V,Krucinska J,Kundracik ML,Wedekind JE

    更新日期:2005-11-08 00:00:00

  • Biosynthesis of the carbohydrate units of immunoglobulins. 1. Purification and properties of galactosyltransferases from swine mesentary lymph nodes.

    abstract::Galactosyltransferase (UDPgalactose:glycoprotein galactosyltransferase EC was isolated from swine mesentary lymhromatography on Sepharose 4B colums containing covalently bound p-aminophenyl-beta-D-N-acetylglucosamine. The homogenous enzyme showed a single band on disc gel electrophoresis and had a specific a...


    pub_type: 杂志文章


    authors: Rao AK,Garver F,Mendicino J

    更新日期:1976-11-16 00:00:00

  • 13C NMR studies of methylene and methine carbons of substrate bound to a 280,000-dalton protein, porphobilinogen synthase.

    abstract::13C NMR has been used to observe the equilibrium complex of [5,5-2H,5-13C]-5-aminolevulinate [( 5,5-2H,5-13C]ALA) bound to porphobilinogen (PBG) synthase (5-aminolevulinate dehydratase), a 280,000-dalton protein. [5,5-2H,5-13C]ALA (chemical shift 46.9 ppm in D2O) was prepared from [5-13C]ALA through enolization in deu...


    pub_type: 杂志文章


    authors: Jaffe EK,Markham GD

    更新日期:1988-06-14 00:00:00

  • O6-methylguanine in DNA inhibits replication in vitro by human cell extracts.

    abstract::To study the effects of methylation damage on DNA replication in vitro, the plasmid pSVori containing the SV40 origin of replication was reacted with N-methyl-N-nitrosourea and used as a substrate for SV40 T antigen dependent replication by HeLa cell extracts. The plasmid was methylated with a range of N-methyl-N-nitr...


    pub_type: 杂志文章


    authors: Ceccotti S,Dogliotti E,Gannon J,Karran P,Bignami M

    更新日期:1993-12-14 00:00:00

  • Characterization of metal ion activation and inhibition of CTP synthetase.

    abstract::A reinvestigation of the metal ion activation and specificity of CTP synthetase was begun in order to separate effects due to binding of free metal ions and binding of nucleotide-complexed ions. Apo-CTP synthetase was prepared by dialysis against 5 mM EDTA. Analysis of apo-enzyme by atomic absorption spectroscopy reve...


    pub_type: 杂志文章


    authors: Robertson JG,Villafranca JJ

    更新日期:1993-04-13 00:00:00

  • Photolabile protecting groups for an acetylcholine receptor ligand. Synthesis and photochemistry of a new class of o-nitrobenzyl derivatives and their effects on receptor function.

    abstract::Two compounds have been synthesized that feature a photosensitive o-nitrobenzyl moiety attached directly to the carbamate nitrogen of carbamoylcholine. The well-characterized acetylcholine analogue, carbamoylcholine, was released from these derivatives in response to laser light pulses at wavelengths between 300 and 3...


    pub_type: 杂志文章


    authors: Walker JW,McCray JA,Hess GP

    更新日期:1986-04-08 00:00:00

  • The Role of Phase Separation in Heterochromatin Formation, Function, and Regulation.

    abstract::In eukaryotic cells, structures called heterochromatin play critical roles in nuclear processes ranging from gene repression to chromosome segregation. Biochemical and in vivo studies over the past several decades have implied that the diverse functions of heterochromatin rely on the ability of these structures to spr...


    pub_type: 杂志文章,评审


    authors: Larson AG,Narlikar GJ

    更新日期:2018-05-01 00:00:00

  • Interfacial and lipid transfer properties of human phospholipid transfer protein: implications for the transfer mechanism of phospholipids.

    abstract::In circulation the phospholipid transfer protein (PLTP) facilitates the transfer of phospholipid-rich surface components from postlipolytic chylomicrons and very low density lipoproteins (VLDL) to HDL and thereby regulates plasma HDL levels. To study the molecular mechanisms involved in PLTP-mediated lipid transfer, w...


    pub_type: 杂志文章


    authors: Setälä NL,Holopainen JM,Metso J,Wiedmer SK,Yohannes G,Kinnunen PK,Ehnholm C,Jauhiainen M

    更新日期:2007-02-06 00:00:00

  • Control of the chemical step by leucine-31 of pancreatic phospholipase A2.

    abstract::A well-defined region of pancreatic and other secreted phospholipase A2 (PLA2), which we call the i-face, makes a molecular contact with the interface to facilitate and control the events and processivity of the interfacial catalytic turnover cycles. The structural features of the i-face and its allosteric relationshi...


    pub_type: 杂志文章


    authors: Yu BZ,Janssen MJ,Verheij HM,Jain MK

    更新日期:2000-05-16 00:00:00

  • Immunochemical analysis of membrane vesicles from Escherichia coli.

    abstract::Membrane vesicles isolated from Escherichia coli ML 308--225 have been analyzed by crossed immunoelectrophoresis, and immunoprecipitates corresponding to the following cellular components have been identified: ATPase (EC 3.6.1,3), two or three NADH dehydrogenases (EC, D-lactate dehydrogenase (EC, g...


    pub_type: 杂志文章


    authors: Owen P,Kaback HR

    更新日期:1979-04-17 00:00:00

  • Preparation and X-ray structures of metal-free, dicobalt and dimanganese forms of soluble methane monooxygenase hydroxylase from Methylococcus capsulatus (Bath).

    abstract::A three-component soluble methane monooxygenase (sMMO) enzyme system catalyzes the hydroxylation of methane to methanol at a carboxylate-bridged diiron center housed in the alpha-subunit of the hydroxylase (MMOH). Catalysis is facilitated by the presence of a regulatory protein (MMOB) and inhibited by MMOD, a protein ...


    pub_type: 杂志文章


    authors: Sazinsky MH,Merkx M,Cadieux E,Tang S,Lippard SJ

    更新日期:2004-12-28 00:00:00

  • Amyloid nucleation triggered by agitation of beta2-microglobulin under acidic and neutral pH conditions.

    abstract::Amyloid nucleation through agitation was studied with beta2-microglobulin, which is responsible for dialysis-related amyloidosis, in the presence of salt under acid and neutral pH conditions. First, the aggregation of beta2-microglobulin in NaCl solutions was achieved by mildly agitating for 24 h at 37 degrees C prote...


    pub_type: 杂志文章


    authors: Sasahara K,Yagi H,Sakai M,Naiki H,Goto Y

    更新日期:2008-02-26 00:00:00

  • Intercalating polycyclic aromatic hydrocarbon-DNA adducts poison DNA religation by Vaccinia topoisomerase and act as roadblocks to digestion by exonuclease III.

    abstract::Polycyclic aromatic hydrocarbon (PAH)-DNA adducts pervert the execution or fidelity of enzymatic DNA transactions and cause mutations and cancer. Here, we examine the effects of intercalating PAH-DNA adducts on the religation reaction of vaccinia DNA topoisomerase, a prototypal type IB topoisomerase (TopIB), and the 3...


    pub_type: 杂志文章


    authors: Yakovleva L,Handy CJ,Yagi H,Sayer JM,Jerina DM,Shuman S

    更新日期:2006-06-20 00:00:00

  • Resonance Raman investigation of nitric oxide bonding in nitrosylhemoglobin A and -myoglobin: detection of bound N-O stretching and Fe-NO stretching vibrations from the hexacoordinated NO-heme complex.

    abstract::With excitation at 406.7 nm, we have observed the resonance Raman enhancement of the bound v(N-O) stretch at approximately 1623 cm-1 in nitrosylhemoglobin A and nitrosylmyoglobin, indicating the existence of a charge-transfer transition underlying the strong Soret band. The v(Fe-NO) stretch at 551 cm-1 has also been d...


    pub_type: 杂志文章


    authors: Tsubaki M,Yu NT

    更新日期:1982-03-16 00:00:00

  • Thermomechanical and transition properties of dimyristoylphosphatidylcholine/cholesterol bilayers.

    abstract::Mixtures of dimyristoylphosphatidylcholine (DMPC) and cholesterol (Chol) have been used to examine the effects of cholesterol on the chain crystallization transitions and thermomechanical properties in phospholipid bilayer membranes. The mechanical properties--elastic moduli and level of tension at membrane rupture--w...


    pub_type: 杂志文章


    authors: Needham D,McIntosh TJ,Evans E

    更新日期:1988-06-28 00:00:00

  • Secretory carrier membrane protein SCAMP2 and phosphatidylinositol 4,5-bisphosphate interactions in the regulation of dense core vesicle exocytosis.

    abstract::Secretory carrier membrane protein 2 (SCAMP2) functions in late steps of membrane fusion in calcium-dependent granule exocytosis. A basic/hydrophobic peptide segment within SCAMP2 (SCAMP2 E: CWYRPIYKAFR) has been implicated in this function and shown to bind and sequester phosphatidylinositol 4,5-bisphosphate [PI(4,5)...


    pub_type: 杂志文章


    authors: Liao H,Ellena J,Liu L,Szabo G,Cafiso D,Castle D

    更新日期:2007-09-25 00:00:00

  • Critical side-chain interactions at a subunit interface in the Arc repressor dimer.

    abstract::In the Arc repressor dimer, the side chains of Ile37 and Val41 in alpha-helix B pack against each other and against the symmetry-related side chains of Ile37' and Val41' in alpha-helix B' to form part of the hydrophobic core and the dimer interface. Following combinatorial mutagenesis of these positions, only the wild...


    pub_type: 杂志文章


    authors: Milla ME,Sauer RT

    更新日期:1995-03-14 00:00:00