School of Chemistry - Research Publications
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ItemNo Preview AvailableStructure of the T109S mutant of Escherichia coli dihydroorotase complexed with the inhibitor 5-fluoroorotate: catalytic activity is reflected by the crystal formLee, M ; Maher, MJ ; Guss, JM (INT UNION CRYSTALLOGRAPHY, 2007-03-01)Crystals of a single-point mutant (T109S) of Escherichia coli dihydroorotase (DHOase) with diminished activity grown in the presence of L-dihydroorotate (L-DHO) are tetragonal, with a monomer in the asymmetric unit. These crystals are extremely unstable and disintegrate shortly after formation, which is followed by the growth of orthorhombic crystals from the remnants of the tetragonal crystals or at new nucleation sites. Orthorhombic crystals, for which a structure has previously been reported [Thoden et al. (2001), Biochemistry, 40, 6989-6997; Lee et al. (2005), J. Mol. Biol. 348, 523-533], contain a dimer of DHOase in the asymmetric unit; the active site of one monomer contains the substrate N-carbamyl-L-aspartate (L-CA-asp) and the active site of the other monomer contains the product of the reaction, L-DHO. In the subunit with L-DHO in the active site, a surface loop (residues 105-115) is 'open'. In the other subunit, with L-CA-asp in the active site, the loop folds inwards, forming specific hydrogen bonds from the loop to the L-CA-asp. The tetragonal crystal form can be stabilized by crystallization in the presence of the inhibitor 5-fluoroorotate (FOA), a product (L-DHO) mimic. Crystals of the complex of T109S DHOase with FOA are tetragonal, space group P4(1)2(1)2, with unit-cell parameters a = b = 72.6, c = 176.1 A. The structure has been refined to R and R(free) values of 0.218 and 0.257, despite severe anisotropy of the diffraction. In this structure, the flexible loops are both in the 'open' conformation, which is consistent with FOA, like L-DHO, binding at both sites. The behaviour of the T109S mutant crystals of DHOase in the presence of L-DHO is explained by initial binding of L-DHO to both subunits, followed by slow conversion to L-CA-asp, with consequent movement of the flexible loop and dissolution of the crystals. Orthorhombic crystals are then able to grow in the presence of L-DHO and L-CA-asp.
ItemNo Preview AvailableSelf-terminating, oxidative radical cyclizationsDreessen, T ; Jargstorff, C ; Lietzau, L ; Plath, C ; Stademann, A ; Wille, U (MDPI, 2004-06-01)The recently discovered novel concept of self-terminating, oxidative radical cyclizations, through which alkynes can be converted into carbonyl compounds under very mild reaction conditions using O-centered inorganic and organic radicals as oxidants, is described.
ItemProtein secretion and outer membrane assembly in AlphaproteobacteriaGatsos, X ; Perry, AJ ; Anwari, K ; Dolezal, P ; Wolynec, PP ; Likic, VA ; Purcell, AW ; Buchanan, SK ; Lithgow, T (OXFORD UNIV PRESS, 2008-11-01)The assembly of beta-barrel proteins into membranes is a fundamental process that is essential in Gram-negative bacteria, mitochondria and plastids. Our understanding of the mechanism of beta-barrel assembly is progressing from studies carried out in Escherichia coli and Neisseria meningitidis. Comparative sequence analysis suggests that while many components mediating beta-barrel protein assembly are conserved in all groups of bacteria with outer membranes, some components are notably absent. The Alphaproteobacteria in particular seem prone to gene loss and show the presence or absence of specific components mediating the assembly of beta-barrels: some components of the pathway appear to be missing from whole groups of bacteria (e.g. Skp, YfgL and NlpB), other proteins are conserved but are missing characteristic domains (e.g. SurA). This comparative analysis is also revealing important structural signatures that are vague unless multiple members from a protein family are considered as a group (e.g. tetratricopeptide repeat (TPR) motifs in YfiO, beta-propeller signatures in YfgL). Given that the process of the beta-barrel assembly is conserved, analysis of outer membrane biogenesis in Alphaproteobacteria, the bacterial group that gave rise to mitochondria, also promises insight into the assembly of beta-barrel proteins in eukaryotes.
ItemThe incidence and outcome of septic shock patients in the absence of early-goal directed therapyHo, BCH ; Bellomo, R ; McGain, F ; Jones, D ; Naka, T ; Wan, L ; Braitberg, G (BIOMED CENTRAL LTD, 2006-01-01)INTRODUCTION: The purpose of the present study was to measure the incidence and outcome of septic patients presenting at the emergency department (ED) with criteria for early goal-directed therapy (EGDT). METHOD: This hospital-based, retrospective, observational study using prospectively collected electronic databases was based in a teaching hospital in Melbourne, Australia. We conducted outcome-blinded electronic screening of patients with infection admitted via the ED from 1 January 2000 to 30 June 2003. We obtained data on demographics, laboratory and clinical features on admission. We used paper records to confirm electronic identification of candidates for EGDT and to study their treatment. We followed up all patients until hospital discharge or death. RESULTS: Of 4,784 ED patients with an infectious disease diagnosis, only 50 fulfilled published clinical inclusion criteria for EGDT (EGDT candidates). Of these patients, 37 (74%) survived their hospital admission, two (4%) died in the ED, eight (16%) died in the intensive care unit and three (6%) died in the ward. After review of all ward cardiac arrests and non-NFR ('not for resuscitation') ward deaths, we identified a further two potential candidates for EGDT for an overall mortality of 28.8% (15 out of 52 patients). Analysis of treatment showed that twice as many (70%) of the EGDT candidates received vasopressor therapy in the ED, and their initial mean central venous pressure (10.8 mmHg) was almost twice that in patients from the EGDT study conducted by Rivers and coworkers. CONCLUSION: In an Australian teaching hospital candidates for EGDT were uncommon and, in the absence of an EGDT protocol, their mortality was lower than that reported with EGDT.
Item2-carboxyquinolinium-2,4,6-trinitro-benzenesulfonate -quinolinium-2-carboxylate (1/1/1)Smith, G ; Wermuth, UD ; White, JM (BLACKWELL PUBLISHING, 2008-01-01)The structure of the title adduct compound, C(10)H(8)NO(2) (+)·C(6)H(2)N(3)O(9)S(-)·C(10)H(7)NO(2), from the reaction of 2,4,6-trinitro-benzene-sulfonic acid (picrylsulfonic acid) with quinoline-2-carboxylic acid (quinaldic acid) in 2-propanol-water, has been determined at 130 (2) K. The cation and the adduct species form a twisted cyclic hydrogen-bonded R(2) (2)(10) pseudo-dimer which is extended into a one-dimensional chain structure through short head-to-tail carboxylic acid O-H⋯O(carbox-yl) associations [O⋯O = 2.4711 (19) Å]. The picrylsulfonate anions are attached peripherally by single N-H⋯O(sulfonate) hydrogen bonds [N⋯O = 2.8643 (19) Å].
ItemMechanisms for the ultrasonic enhancement of dairy whey ultrafiltrationMuthukumaran, S ; Kentish, SE ; Ashokkumar, M ; Stevens, GW (ELSEVIER SCIENCE BV, 2005-08-01)
ItemThe use of ultrasonic cleaning for ultrafiltration membranes in the dairy industryMuthukumaran, S ; Yang, K ; Seuren, A ; Kentish, S ; Ashokkumar, M ; Stevens, GW ; Grieser, F (ELSEVIER SCIENCE BV, 2004-10-01)
ItemNo Preview Available2-DIMENSIONAL DIFFUSION OF AMPHIPHILES IN PHOSPHOLIPID MONOLAYERS AT THE AIR-WATER-INTERFACECARUSO, F ; GRIESER, F ; THISTLETHWAITE, PJ ; ALMGREN, M (CELL PRESS, 1993-12-01)Steady-state and time-resolved fluorescence spectroscopy has been used to examine lateral diffusion in dipalmitoyl-L-alpha-phosphatidylcholine (DPPC) and dimyristoyl-L-alpha-phosphatidylcholine (DMPC) monolayers at the air-water interface, by studying the fluorescence quenching of a pyrene-labeled phospholipid (pyrene-DPPE) by two amphiphilic quenchers. Steady-state fluorescence measurements revealed pyrene-DPPE to be homogeneously distributed in the DMPC lipid matrix for all measured surface pressures and only in the liquid-expanded (LE) phase of the DPPC monolayer. Time-resolved fluorescence decays for pyrene-DPPE in DMPC and DPPC (LE phase) in the absence of quencher were best described by a single-exponential function, also suggesting a homogeneous distribution of pyrene-DPPE within the monolayer films. Addition of quencher to the monolayer film produced nonexponential decay behavior, which is adequately described by the continuum theory of diffusion-controlled quenching in a two-dimensional environment. Steady-state fluorescence measurements yielded lateral diffusion coefficients significantly larger than those obtained from time-resolved data. The difference in these values was ascribed to the influence of static quenching in the case of the steady-state measurements. The lateral diffusion coefficients obtained in the DMPC monolayers were found to decrease with increasing surface pressure, reflecting a decrease in monolayer fluidity with compression.
ItemNo Preview AvailableNational Chemistry Week Roadshow and other Outreach ActivitiesMOYLAN, M ; Clark, M (Royal Australian Chemical Institute, 2005)
ItemEffect of surfactants on the rate of growth of an air bubble by rectified diffusionLee, J ; Kentish, S ; Ashokkumar, M (AMER CHEMICAL SOC, 2005-08-04)The rectified diffusion growth of a single air bubble levitated in an acoustic field (frequency = 22.35 kHz) in water and in aqueous solutions containing surfactants (sodium dodecyl sulfate and sodium dodecylbenzene sulfonate) was investigated. As reported by Crum (J. Acoust. Soc. Am. 1980, 68, 203), the presence of surfactants at the bubble/liquid interface enhanced the growth rate of the bubble by rectified diffusion. It is suggested in this paper that in addition to the effect of surfactants on the surface tension and interfacial resistance to mass transfer, the effect of surface rheological properties may also contribute to the cause of the enhancement observed in the bubble growth rate.
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