PubMed Health⌕ Search

Biomedical subjects

G Auger

Publications and source records attributed to G Auger.

At least 19 recordsLinked to original sources

Isotopic scaling and the symmetry energy in spectator fragmentation.

Isotopic effects in the fragmentation of excited target residues following collisions of 12C on (112,124)Sn at incident energies of 300 and 600 MeV per nucleon were studied with the INDRA 4pi detector. The measured yield ratios for light particles and fragments with atomic number Z < or = 5 obey the exponential law of isotopic scaling. The deduced scaling parameters decrease strongly with increasing centrality to values smaller than 50% of those obtained for the peripheral event groups. Symmetry-term coefficients, deduced from these data within the statistical description of isotopic scaling, are near gamma = 25 MeV for peripheral and gamma < 15 MeV for central collisions.

Journal Article↗

Evidence for spinodal decomposition in nuclear multifragmentation.

Multifragmentation of a "fused system" was observed for central collisions between 32 MeV/nucleon 129Xe and (nat)Sn. Most of the resulting charged products were well identified due to the high performances of the INDRA 4pi array. Experimental higher-order charge correlations for fragments show a weak but nonambiguous enhancement of events with nearly equal-sized fragments. Supported by dynamical calculations in which spinodal decomposition is simulated, this observed enhancement is interpreted as a "fossil" signal of spinodal instabilities in finite nuclear systems.

Journal Article↗

Evidence of a functional requirement for a carbamoylated lysine residue in MurD, MurE and MurF synthetases as established by chemical rescue experiments.

Enzymes MurD, MurE, MurF, folylpolyglutamate synthetase and cyanophycin synthetase, which belong to the Mur synthetase superfamily, possess an invariant lysine residue (K198 in the Escherichia coli MurD numbering). Crystallographic analysis of MurD and MurE has recently shown that this residue is present as a carbamate derivative, a modification presumably essential for Mg(2+) binding and acyl phosphate formation. In the present work, the importance of the carbamoylated residue was investigated in MurD, MurE and MurF by site-directed mutagenesis and chemical rescue experiments. Mutant proteins MurD K198A/F, MurE K224A and MurF K202A, which displayed low enzymatic activity, were rescued by incubation with short-chain carboxylic acids, but not amines. The best rescuing agent was acetate for MurD K198A, formate for K198F, and propionate for MurE K224A and MurF K202A. In the last of these, wild-type levels of activity were recovered. A complementarity between the volume of the residue replacing lysine and the length of the carbon chain of the acid was noted. These observations support a functional role for the carbamate in the three Mur synthetases. Experiments aimed at recovering an active enzyme by introducing an acidic residue in place of the invariant lysine residue were also undertaken. Mutant protein MurD K198E was weakly active and was rescued by formate, indicating the necessity of correct positioning of the acidic function with respect to the peptide backbone. Attempts at covalent rescue of mutant protein MurD K198C failed because of its lack of reactivity towards haloacids.

Base Sequence↗

Interaction of bacterial lipopolysaccharide with mouse surfactant protein C inserted into lipid vesicles.

Infection of the respiratory tract is a frequent cause of lung pathologies, morbidity, and death. When bacterial endotoxin [lipopolysaccharide (LPS)] reaches the alveolar spaces, it encounters the lipid-rich surfactant that covers the epithelium. Although binding of hydrophilic surfactant protein (SP) A and SP-D with LPS has been established, nothing has been reported to date on possible cross talks between LPS and hydrophobic SP-B and SP-C. We designed a new binding technique based on the incorporation of surfactant components to lipid vesicles and the separation of unbound from vesicle-bound LPS on a density gradient. We found that among the different hydrophobic components of mouse surfactant separated by gel filtration or reverse-phase HPLC, only SP-C exhibited the capacity to bind to a tritium-labeled LPS. The binding of LPS to vesicles containing SP-C was saturable, temperature dependent, related to the concentrations of SP-C and LPS, and inhibitable by distinct unlabeled LPSs. Unlike SP-A and SP-D, the binding of SP-C to LPS did not require calcium ions. This LPS binding capacity of SP-C may represent another antibacterial defense mechanism of the lung.

Animals↗

"Open" structures of MurD: domain movements and structural similarities with folylpolyglutamate synthetase.

UDP-N-acetylmuramoyl-l-alanine:d-glutamate (MurD) ligase catalyses the addition of d-glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-l-alanine (UMA). The crystal structures of Escherichia coli in the substrate-free form and MurD complexed with UMA have been determined at 2.4 A and 1.88 A resolution, respectively. The MurD structure comprises three domains each of a topology reminiscent of nucleotide-binding folds. In the two structures the C-terminal domain undergoes a large rigid-body rotation away from the N-terminal and central domains. These two "open" structures were compared with the four published "closed" structures of MurD. In addition the comparison reveals which regions are affected by the binding of UMA, ATP and d-Glu. Also we compare and discuss two structurally characterized enzymes which belong to the same ligase superfamily: MurD and folylpolyglutamate synthetase (FGS). The analysis allows the identification of key residues involved in the reaction mechanism of FGS. The determination of the two "open" conformation structures represents a new step towards the complete elucidation of the enzymatic mechanism of the MurD ligase.

Adenosine Triphosphate↗

Shape coexistence and the N = 28 shell closure far from stability

The masses of 31 neutron-rich nuclei in the range A = 29-47 have been measured. The precision of 19 masses has been significantly improved and 12 masses were measured for the first time. The neutron-rich Cl, S, and P isotopes are seen to exhibit a change in shell structure around N = 28. Comparison with shell model and relativistic mean field calculations demonstrate that the observed effects arise from deformed prolate ground state configurations associated with shape coexistence. Evidence for shape coexistence is provided by the observation of an isomer in 43S.

Journal Article↗

Determination of the MurD mechanism through crystallographic analysis of enzyme complexes.

UDP -N- acetylmuramoyl- L -alanine: D -glutamate (MurD) ligase catalyses the addition of d -glutamate to the nucleotide precursor UDP -N- acetylmuramoyl- L -alanine (UMA). The crystal structures of three complexes of Escherichia coli MurD with a variety of substrates and products have been determined to high resolution. These include (1) the quaternary complex of MurD, the substrate UMA, the product ADP, and Mg2+, (2) the quaternary complex of MurD, the substrate UMA, the product ADP, and Mn2+, and (3) the binary complex of MurD with the product UDP - N- acetylmuramoyl- L -alanine- D -glutamate (UMAG). The reaction mechanism supported by these structures proceeds by the phosphorylation of the C-terminal carboxylate group of UMA by the gamma-phosphate group of ATP to form an acyl-phosphate intermediate, followed by the nucleophilic attack by the amino group of D-glutamate to produce UMAG. A key feature in the reaction intermediate is the presence of two magnesium ions bridging negatively charged groups.

Adenosine Diphosphate↗

A comparative analysis of arranging in-flight oxygen aboard commercial air carriers.

INTRODUCTION: As air travel has become more commonplace in today's society, so too has air travel by oxygen-using individuals. Because there is little oversight or standardization of in-flight oxygen by the Federal Aviation Administration, individual airlines' policies and practices may vary greatly. On the premise that such variation may cause confusion by prospective air travelers, we undertook the current study to describe individual air carriers' policies and practices and to provide guidance to future air travelers. METHODS: Data were collected by a series of telephone calls placed by the study investigators to all commercial air carriers listed in the 1997 Cleveland Metropolitan Yellow Pages. The callers were registered respiratory therapists who identified themselves as inexperienced oxygen-requiring travelers wishing to arrange in-flight oxygen for an upcoming trip. Standard questions were asked of each carrier that included the following: Did the carrier have a special "help desk" to assist with oxygen arrangements? What oxygen systems, liter flow options, and interface devices were available? What was the charge for oxygen? How was the charged determined? What documentation from the physician was required? How much notification was required by the airline before the actual flight? In addition to recording these responses, the total amount of time spent on the telephone by the caller was logged along with the number of telephone calls and number of people spoken to in arranging in-flight oxygen. To compare oxygen charges between airlines, we calculated charges based on a "standard trip," which was defined as a nonstop, round-trip lasting 6 h in which the traveler used a flow rate of 2 L/min. RESULTS: Of the 33 commercial air carriers listed in the directory, 11 were US-based carriers and 22 were international-based carriers. Seventy-six percent of the airlines offered in-flight oxygen. For the 25 carriers offering in-flight oxygen, mean phone time required to make the arrangements was 9.96+/-4.8 min (range, 3 to 20 min). No more than two telephone calls were required to make oxygen arrangements. Most carriers required 48- to 72-h advance notice, with a single carrier requiring 1-month advance notice. Most carriers required some notification of oxygen needs by the traveler's physician. There was a great variation in oxygen device and liter flow availability. Liter flow options ranged from only two flow rates (36% of carriers) to a range of 1 to 15 L/min (one carrier). All carriers offered nasal cannula, which was the only device available for 21 carriers (84%). Actual charges for in-flight oxygen also varied greatly. Six carriers supplied oxygen free and 18 carriers charged a fee (range, $64 to $1,500). One airline allowed the traveler to bring one "E" cylinder with no fee assessed. For 14 of the 18 carriers that charged, the charge for the standard trip ranged from $100 to $250. CONCLUSIONS: (1) As expected from the lack of standard regulations, the availability, costs, and ease of implementing in-flight oxygen vary greatly among commercial air carriers. (2) Because the expense of in-flight oxygen is usually borne by the traveler (rather than by insurers), prospective travelers should consider charges for oxygen use when choosing an airline. (3) In the context that the current study shows substantial variation in oxygen policies, costs, and services among commercial air carriers and that such policies may change over time, our findings encourage the prospective air traveler needing in-flight oxygen to "shop around."

Aircraft↗

Large-scale preparation, purification, and crystallization of UDP-N-acetylmuramoyl-L-alanine: D-glutamate ligase from Escherichia coli.

The UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase from Escherichia coli, an enzyme involved in the biosynthesis of the bacterial peptidoglycan monomer unit, was overproduced and purified to homogeneity on a large scale, yielding 4 mg of protein per liter of bacterial culture. Crystals of the complex with the substrate UDP-MurNAc-L-Ala were grown by the hanging drop method using ammonium sulfate as the precipitant. They are tetragonal with cell dimensions a = b = 65.5 A and c = 134.59 A, space group P4(1) or P4(3), and contain one monomer of 46,842 Da in the asymmetric unit. In order to use the multiple-wavelength anomalous diffraction method for phasing, a selenomethionine derivative of the protein has also been overproduced, purified, and crystallized.

Amino Acid Sequence↗

Crystal structure of UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase from Escherichia coli.

UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (MurD) is a cytoplasmic enzyme involved in the biosynthesis of peptidoglycan which catalyzes the addition of D-glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine (UMA). The crystal structure of MurD in the presence of its substrate UMA has been solved to 1.9 A resolution. Phase information was obtained from multiple anomalous dispersion using the K-shell edge of selenium in combination with multiple isomorphous replacement. The structure comprises three domains of topology each reminiscent of nucleotide-binding folds: the N- and C-terminal domains are consistent with the dinucleotide-binding fold called the Rossmann fold, and the central domain with the mononucleotide-binding fold also observed in the GTPase family. The structure reveals the binding site of the substrate UMA, and comparison with known NTP complexes allows the identification of residues interacting with ATP. The study describes the first structure of the UDP-N-acetylmuramoyl-peptide ligase family.

Adenosine Triphosphate↗

Effect of analogues of diaminopimelic acid on the meso-diaminopimelate-adding enzyme from Escherichia coli.

Several analogues of diaminopimelic acid (A2pm) were tested as substrates or inhibitors of the meso-diaminopimelate-adding enzyme from Escherichia coli. They included lanthionine derivatives, a phosphonic analogue, heterocyclic compounds, 3-fluoro-A2pm, 4-methylene-A2pm and N-hydroxy-A2pm. The best substrates were, in decreasing order of specific enzyme activity, (2S,3R,6S)-3-fluoro-A2pm, meso-lanthionine sulfoxide and N-hydroxy-A2pm (mixture of stereoisomers). In those cases where all the stereoisomers were available, the specificity could be described as meso > > DD approximately to LL. N-Hydroxy-A2pm (mixture of stereoisomers) strongly inhibited the addition of radioactive meso-A2pm to UDP-N-acetylmuramoyl-dipeptide.

Diaminopimelic Acid↗