Crystal structure of homoserine transacetylase from Haemophilus influenzae reveals a new family of alpha/beta-hydrolases.


:Homoserine transacetylase catalyzes one of the required steps in the biosynthesis of methionine in fungi and several bacteria. We have determined the crystal structure of homoserine transacetylase from Haemophilus influenzae to a resolution of 1.65 A. The structure identifies this enzyme to be a member of the alpha/beta-hydrolase structural superfamily. The active site of the enzyme is located near the end of a deep tunnel formed by the juxtaposition of two domains and incorporates a catalytic triad involving Ser143, His337, and Asp304. A structural basis is given for the observed double displacement kinetic mechanism of homoserine transacetylase. Furthermore, the properties of the tunnel provide a rationale for how homoserine transacetylase catalyzes a transferase reaction vs hydrolysis, despite extensive similarity in active site architecture to hydrolytic enzymes.






Mirza IA,Nazi I,Korczynska M,Wright GD,Berghuis AM




Has Abstract


2005-12-06 00:00:00












  • Temperature dependence of the structure of the substrate and active site of the Thermus thermophilus chorismate mutase E x S complex.

    abstract::Molecular dynamics (MD) simulations of Thermus thermophilus chorismate mutase substrate complex (TtCM x S) have been carried out at 298 K, 333 K, and the temperature of optimum activity: 343 K. The enzyme exists as trimeric subunits with active sites shared between two neighboring subunits. Two features distinguish in...


    pub_type: 杂志文章


    authors: Zhang X,Bruice TC

    更新日期:2006-07-18 00:00:00

  • Identification of BECN1 and ATG14 Coiled-Coil Interface Residues That Are Important for Starvation-Induced Autophagy.

    abstract::Autophagy, an essential eukaryotic homeostasis pathway, allows the sequestration of unwanted, damaged, or harmful cytoplasmic components in vesicles called autophagosomes, permitting subsequent lysosomal degradation and nutrient recycling. Autophagosome nucleation is mediated by class III phosphatidylinositol-3-kinase...


    pub_type: 杂志文章


    authors: Mei Y,Su M,Sanishvili R,Chakravarthy S,Colbert CL,Sinha SC

    更新日期:2016-08-02 00:00:00

  • Identification and metabolic transformations of carotenoids in ocular tissues of the Japanese quail Coturnix japonica.

    abstract::As in humans and monkeys, lutein [(3R,3'R,6'R)-beta,epsilon-carotene-3,3'-diol] and zeaxanthin [a mixture of (3R,3'R)-beta,beta-carotene-3,3'diol and (3R,3'S-meso)-beta,beta-carotene-3,3'-diol] are found in substantial amounts in the retina of the Japanese quail Coturnix japonica. This makes the quail retina an excell...


    pub_type: 杂志文章


    authors: Bhosale P,Serban B,Zhao DY,Bernstein PS

    更新日期:2007-08-07 00:00:00

  • The role of the specificity-determining loop of the integrin beta subunit I-like domain in autonomous expression, association with the alpha subunit, and ligand binding.

    abstract::Integrin beta subunits contain a highly conserved I-like domain that is known to be important for ligand binding. Unlike integrin I domains, the I-like domain requires integrin alpha and beta subunit association for optimal folding. Pactolus is a novel gene product that is highly homologous to integrin beta subunits b...


    pub_type: 杂志文章


    authors: Takagi J,DeBottis DP,Erickson HP,Springer TA

    更新日期:2002-04-02 00:00:00

  • Acyclic guanosine analogs inhibit DNA polymerases alpha, delta, and epsilon with very different potencies and have unique mechanisms of action.

    abstract::Acyclovir triphosphate, ganciclovir triphosphate and penciclovir triphosphate inhibited DNA polymerases alpha, delta, and epsilon. Each triphosphate preferentially inhibited pol delta, although ganciclovir triphosphate was the most impressive of the three; the Ki for inhibition of pol delta was 2 microM (competitive w...


    pub_type: 杂志文章


    authors: Ilsley DD,Lee SH,Miller WH,Kuchta RD

    更新日期:1995-02-28 00:00:00

  • Investigations of photolysis and rebinding kinetics in myoglobin using proximal ligand replacements.

    abstract::We use laser flash photolysis and time-resolved Raman spectroscopy of CO-bound H93G myoglobin (Mb) mutants to study the influence of the proximal ligand on the CO rebinding kinetics. In H93G mutants, where the proximal linkage with the protein is eliminated and the heme can bind exogenous ligands (e.g., imidazole, 4-b...


    pub_type: 杂志文章


    authors: Cao W,Ye X,Sjodin T,Christian JF,Demidov AA,Berezhna S,Wang W,Barrick D,Sage JT,Champion PM

    更新日期:2004-08-31 00:00:00

  • Conformational flexibility of luteinizing hormone-releasing hormone in aqueous solution. A carbon-13 spin-lattice relaxation time study.

    abstract::The carbon-13 nuclear magnetic resonance (13C NMR) spectra of luteinizing hormone-releasing hormone (LH-RH) and lower homologous peptides have been assigned in aqueous solutions at various pH values. 13C spin-lattice relaxation times (T1) have been measured for all proton-bearing carbons at 25.2 and 67.9 MHz. From the...


    pub_type: 杂志文章


    authors: Deslauriers R,Levy GC,McGregor WH,Sarantakis K,Smith IC

    更新日期:1975-09-23 00:00:00

  • Intrinsic fluorescence reports a global conformational change in the N-lobe of human serum transferrin following iron release.

    abstract::Transferrins have been extensively studied in order to understand how they reversibly bind and release iron. Human serum transferrin (hTF) is a single polypeptide chain that folds into two lobes (N- and C-lobe); each lobe binds a single ferric ion. Iron release induces a large conformational change in each lobe. At th...


    pub_type: 杂志文章


    authors: James NG,Berger CL,Byrne SL,Smith VC,MacGillivray RT,Mason AB

    更新日期:2007-09-18 00:00:00

  • Coupling of transmembrane helix orientation to membrane release of the juxtamembrane region in FGFR3.

    abstract::Activation of the protein tyrosine kinase receptors requires the coupling of ligand binding to a change in both the proximity and orientation of the single transmembrane (TM) helices of receptor monomers to allow transphosphorylation of the receptor kinase domain. We make use of peptides corresponding to the TM and ju...


    pub_type: 杂志文章


    authors: Tamagaki H,Furukawa Y,Yamaguchi R,Hojo H,Aimoto S,Smith SO,Sato T

    更新日期:2014-08-05 00:00:00

  • Interconversion of conformational isomers of light chains in the Mcg immunoglobulins.

    abstract::Previous crystallographic studies in this laboratory demonstrated that immunoglobulin light chains with the same amino acid sequence can have at least two and probably three or more conformations, depending on whether the second member of an interacting pair is a light or heavy chain. If a heavy chain is not available...


    pub_type: 杂志文章


    authors: Firca JR,Ely KR,Kremser P,Westholm FA,Dorrington KJ,Edmundson AB

    更新日期:1978-01-10 00:00:00

  • Looking at human cytosolic sialidase NEU2 structural features with an interdisciplinary approach.

    abstract::Circular dichroism (CD) spectra at variable temperatures have been recorded for human cytosolic sialidase NEU2 in buffered water solutions and in the presence of divalent cations. The results show the prevalence of β-strands together with a considerable amount of α-helical structure, while in the solid state, from bot...


    pub_type: 杂志文章


    authors: Monti E,Benaglia G,Mozzi A,Fusi P,Longhi G,Gangemi F,Castiglioni E,Woody RW,Fornili SL,Abbate S

    更新日期:2014-08-19 00:00:00

  • Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme.

    abstract::We have systematically validated the activity and inhibition of a HIV-1 protease (PR) variant bearing 17 mutations (PR(S17)), selected to represent high resistance by machine learning on genotype-phenotype data. Three of five mutations in PR(S17) correlating with major drug resistance, M46L, G48V, and V82S, and five o...


    pub_type: 杂志文章


    authors: Park JH,Sayer JM,Aniana A,Yu X,Weber IT,Harrison RW,Louis JM

    更新日期:2016-04-26 00:00:00

  • Apical membrane of the gastric parietal cell: water, proton, and nonelectrolyte permeabilities.

    abstract::Gastric parietal cell apical membranes must protect the cell from the extremely low pH and wide variations in osmolality of the gastric juice. To characterize the permeability properties of gastric apical membranes, we have measured passive permeabilities to water, protons, NH3, and small nonelectrolytes of membrane v...


    pub_type: 杂志文章


    authors: Priver NA,Rabon EC,Zeidel ML

    更新日期:1993-03-16 00:00:00

  • Structure and cholesterol dynamics of caveolae/raft and nonraft plasma membrane domains.

    abstract::Despite recognition that the plasma membrane (PM) is comprised of lipid raft domains that are key organizing sites of multiple signaling pathways and other cell functions, limited information is available regarding the structure and function in sterol dynamics of these microdomains. To begin to resolve these issues, M...


    pub_type: 杂志文章


    authors: Gallegos AM,Storey SM,Kier AB,Schroeder F,Ball JM

    更新日期:2006-10-03 00:00:00

  • Hydrophobic core of the steroidogenic acute regulatory protein for cholesterol transport.

    abstract::The steroidogenic acute regulatory protein (StAR), the first family member of START (StAR-related lipid transport) proteins, plays an essential role by facilitating the movement of cholesterol from the outer to inner mitochondrial membrane. Wild-type and mutant StAR binds cholesterol with similar intensity, but only w...


    pub_type: 杂志文章


    authors: Bose HS,Whittal RM,Bose M,Debnath D

    更新日期:2009-02-17 00:00:00

  • pH dependence of the inhibition of chymotrypsin by a peptidyl trifluoromethyl ketone.

    abstract::The effects of pH on the kinetics of association and dissociation of chymotrypsin and the dipeptidyl trifluoromethyl ketone (TFK) N-acetyl-L-leucyl-L-phenylalanyltrifluoromethane (1) were examined through the pH range 4-9.5. The pH dependence of the association rate (kon) is similar to that of kcat/Km for ester and pe...


    pub_type: 杂志文章


    authors: Brady K,Liang TC,Abeles RH

    更新日期:1989-11-14 00:00:00

  • Reevaluation of the stoichiometry of cytochrome b559 in photosystem II and thylakoid membranes.

    abstract::The stoichiometry of cytochrome b559 (one or two copies) per reaction center of photosystem II (PSII) has been the subject of considerable debate. The molar ratio of cytochrome b559 has a number of significant implications on our understanding of the functional role of cytochrome b559, the mechanism of electron donati...


    pub_type: 杂志文章


    authors: Buser CA,Diner BA,Brudvig GW

    更新日期:1992-11-24 00:00:00

  • Structural studies of P22 phage, precursor particles, and proteins by laser Raman spectroscopy.

    abstract::For the study of the protein--protein and protein--nucleic acid interactions in the assembly of virus particles, laser Raman spectra have been obtained in H2O and D2O solutions and as a function of temperature for the following Salmonella phage P22 components: mature phage particles, isolated mature phage DNA, mature ...


    pub_type: 杂志文章


    authors: Thomas GJ Jr,Li Y,Fuller MT,King J

    更新日期:1982-08-03 00:00:00

  • In vitro biosynthesis of UDP-N,N'-diacetylbacillosamine by enzymes of the Campylobacter jejuni general protein glycosylation system.

    abstract::In Campylobacter jejuni 2,4-diacetamido-2,4,6-trideoxy-alpha-d-glucopyranose, termed N,N'-diacetylbacillosamine (Bac2,4diNAc), is the first carbohydrate in the glycoprotein N-linked heptasaccharide. With uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) as a starting point, two enzymes of the general protein glycos...


    pub_type: 杂志文章


    authors: Olivier NB,Chen MM,Behr JR,Imperiali B

    更新日期:2006-11-14 00:00:00

  • Mechanism of zinc coordination by point-mutated structures of the distal CCHC binding motif of the HIV-1 NCp7 protein.

    abstract::The kinetics of Zn(2+) binding by two point-mutated forms of the HIV-1 NCp7 C-terminal zinc finger, each containing tridentate binding motif HCC [Ser49(35-50)NCp7] or CCC [Ala44(35-50)NCp7], has been studied by stopped-flow spectrofluorimetry. Both the formation and dissociation rate constants of the complexes between...


    pub_type: 杂志文章


    authors: Bombarda E,Roques BP,Mély Y,Grell E

    更新日期:2005-05-17 00:00:00

  • Crystal structure of the DNA decamer d(CGCAATTGCG) complexed with the minor groove binding drug netropsin.

    abstract::The crystal structure of netropsin bound to the decamer d(CGCAATTGCG) has been determined at 2.4 A resolution. This is the first example of a crystal structure of netropsin bound to decamer DNA. The central eight bases of each DNA single-strand base pair with a self-complementary strand to form an octamer B-DNA duplex...


    pub_type: 杂志文章


    authors: Nunn CM,Garman E,Neidle S

    更新日期:1997-04-22 00:00:00

  • Rhodamine 123 binds to multiple sites in the multidrug resistance protein (MRP1).

    abstract::The mechanisms of MRP1-drug binding and transport are not clear. In this study, we have characterized the interaction between MRP1 and rhodamine 123 (Rh123) using the photoreactive-iodinated analogue, [(125)I]iodoaryl azido-rhodamine 123 (or IAARh123). Photoaffinity labeling of plasma membranes from HeLa cells transfe...


    pub_type: 杂志文章


    authors: Daoud R,Kast C,Gros P,Georges E

    更新日期:2000-12-19 00:00:00

  • Metamorphic response of the CLIC1 chloride intracellular ion channel protein upon membrane interaction.

    abstract::A striking feature of the CLIC (chloride intracellular channel) protein family is the ability of its members to convert between a soluble state and an integral membrane channel form. Direct evidence of the structural transition required for the CLIC protein to autonomously insert into the membrane is lacking, largely ...


    pub_type: 杂志文章


    authors: Goodchild SC,Howell MW,Littler DR,Mandyam RA,Sale KL,Mazzanti M,Breit SN,Curmi PM,Brown LJ

    更新日期:2010-06-29 00:00:00

  • Insulin signaling in the yeast Saccharomyces cerevisiae. 1. Stimulation of glucose metabolism and Snf1 kinase by human insulin.

    abstract::Effects of human insulin on glucose metabolism in the yeast Saccharomyces cerevisiae were studied in this report. Under two conditions of growth limitation (glucose-grown cells during transition to stationary phase or spheroplasts during incubation in synthetic glucose medium), human insulin (10 and 1 microM, respecti...


    pub_type: 杂志文章


    authors: Müller G,Rouveyre N,Crecelius A,Bandlow W

    更新日期:1998-06-16 00:00:00

  • Structure of human transferrin receptor oligosaccharides: conservation of site-specific processing.

    abstract::The human transferrin receptor (TfR) has three N-linked oligosaccharides. A combination of site-directed mutagenesis and carbohydrate and protein chemistry was used to characterize the structures of the N-linked oligosaccharides and to map their locations. We find that the type of oligosaccharide at each position was ...


    pub_type: 杂志文章


    authors: Hayes GR,Williams AM,Lucas JJ,Enns CA

    更新日期:1997-04-29 00:00:00

  • Structural basis for hydration dynamics in radical stabilization of bilin reductase mutants.

    abstract::Heme-derived linear tetrapyrroles (phytobilins) in phycobiliproteins and phytochromes perform critical light-harvesting and light-sensing roles in oxygenic photosynthetic organisms. A key enzyme in their biogenesis, phycocyanobilin:ferredoxin oxidoreductase (PcyA), catalyzes the overall four-electron reduction of bili...


    pub_type: 杂志文章


    authors: Kohler AC,Gae DD,Richley MA,Stoll S,Gunn A,Lim S,Martin SS,Doukov TI,Britt RD,Ames JB,Lagarias JC,Fisher AJ

    更新日期:2010-07-27 00:00:00

  • Nanosecond fluorescence studies of noncovalent interaction of monomeric and dimeric intercalators with DNA.

    abstract::The noncovalent interaction of 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) and its derivatives, which are potent mutagens isolated from L-glutamic acid pyrolysate, with calf thymus DNA was studied by steady-state and nanosecond fluorescence spectroscopies. The fluorescence of these compounds exhibits static quen...


    pub_type: 杂志文章


    authors: Itoh M,Kurokawa H,Usui M,Ohno M,Shimoda E,Hashimoto Y,Shudo K

    更新日期:1985-11-05 00:00:00

  • Kinetic, crystallographic, and mechanistic characterization of TomN: elucidation of a function for a 4-oxalocrotonate tautomerase homologue in the tomaymycin biosynthetic pathway.

    abstract::The biosynthesis of the C ring of the antitumor antibiotic agent, tomaymycin, is proposed to proceed through five enzyme-catalyzed steps from l-tyrosine. The genes encoding these enzymes have recently been cloned and their functions tentatively assigned, but there is limited biochemical evidence supporting the assignm...


    pub_type: 杂志文章


    authors: Burks EA,Yan W,Johnson WH Jr,Li W,Schroeder GK,Min C,Gerratana B,Zhang Y,Whitman CP

    更新日期:2011-09-06 00:00:00

  • Pathways of Metabolite-Related Damage to a Synthetic p53 Gene Exon 7 Oligonucleotide Using Magnetic Enzyme Bioreactor Beads and LC-MS/MS Sequencing.

    abstract::Reactive metabolites of environmental chemicals and drugs can cause site specific damage to the p53 tumor suppressor gene in a major pathway for genotoxicity. We report here a high-throughput, cell-free, 96-well plate magnetic bead-enzyme system interfaced with LC-MS/MS sequencing for bioactivating test chemicals and ...


    pub_type: 杂志文章


    authors: Malla S,Kadimisetty K,Jiang D,Choudhary D,Rusling JF

    更新日期:2018-07-03 00:00:00

  • Kinetics of long-chain (sphingoid) base biosynthesis in intact LM cells: effects of varying the extracellular concentrations of serine and fatty acid precursors of this pathway.

    abstract::Serine palmitoyltransferase (EC catalyzes the condensation of L-serine and palmitoyl-CoA to yield 3-ketosphinganine in the first unique reaction of long-chain (sphingoid) base biosynthesis. The kinetic effects of changing the extracellular concentrations of the precursors for this pathway were studied with L...


    pub_type: 杂志文章


    authors: Merrill AH Jr,Wang E,Mullins RE

    更新日期:1988-01-12 00:00:00