Crystal structure of the amino-terminal fragment of vaccinia virus DNA topoisomerase I at 1.6 å resolution

Sharma, Amit; Hanai, Ryo; Mondragón, Alfonso

doi:10.1016/s0969-2126(94)00077-8

Cited by 66 publications

(74 citation statements)

References 38 publications

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“…In addition, we quantify the accuracy of the integrators by measuring the fluctuation of energy and the temperature of the entire system or its subsystems. The simulations are conducted near the temperature of 300 K for 1VCC, a protein fragment of Vaccinia virus DNA topoisomerase in water [16]. The system is made up of 26,228 atoms, of which 24,963 comprise the water.…”

Section: Numerical Examples In the Microcanonical Andmentioning

confidence: 99%

Computationally efficient molecular dynamics integrators with improved sampling accuracy

et al. 2012

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The design of numerical integrators for particle simulations with arbitrary potentials entails fundamental tradeoffs between the accuracy achieved and the amount of computation required. Here we introduce a class of explicit variational integrators designed to achieve high accuracy for quadratic potentials, with little additional computation relative to traditional integrators. We show that, in practice, these new integrators also improve accuracy for classical biomolecular simulations, since the potential in the vicinity of a typical trajectory point in such a simulation is generally well modelled by a quadratic well. In particular, these integrators provide better sampling accuracy for biomolecular simulation than the commonly used Verlet integrators, as indicated by a weaker dependence of simulated ensemble properties on the time step. They also reduce short-timescale energy fluctuations, thus substantially improving the efficiency of Hybrid Monte Carlo methods, and are easy to implement through straightforward modification of codes based on Verlet integrators.

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Section: Numerical Examples In the Microcanonical Andmentioning

confidence: 99%

Computationally efficient molecular dynamics integrators with improved sampling accuracy

et al. 2012

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“…Thus, only a limited number of experiments were performed using this technique in its original form (Madden, Gorga, Strominger & Wiley, 1992;Silver, Guo, Strominger & Wiley, 1992;Clark, Halay, Lai & Burley, 1993;Kim & Lipscomb, 1993;Bullock, Branchaud & Remingtonk, 1994;Andersen, Thirup, Nyborg, Dolmer, Jacobsen & Sottrup-Jensen, 1994;Watowich, Skehel & Wiley, 1995). Replacement of the wire by other materials such as glass (Burmeister, Huber & Bjorkman, 1994;Huber, Wang, Bieber & Bjorkman, 1994;Brown, Jardetzky, Gorga, Stern, Urban, Strominger & Wiley, 1993), hair (Bennett & Eisenberg, 1994) or synthetic or natural fibres such as rayon, mohair or dental floss (Sharma, Hanai & Mondragon, 1994;Djinovic-Carugo, Battiston, Carri, Polticelli, Desideri, Rotilio, Coda & Bolognesi, 1994;Brown, Jardetzky, Stern, Gorga, Strominger & Wiley, 1995;Owen, Noble, Garman, Papageorgiou & Johnson, 1995) alleviated this problem and the method has become increasingly popular and widely used (e.g. Bullough, Hughson, Treharne, Ruigrok, Skehel & Wiley, 1994;Oubridge, Nobutoshi, Evans, Teo & Nagai, 1994;Mattevi, Valentini, Rizzi, Speranza, Bolognesi & Coda, 1995;Rodgers, Gamblin, Harris, Ray, Culp, Hellmig, Woolf, Debouck & Harrison, 1995;Reinisch, Chen, Verdine & Lispcomb, 1995).…”

Section: Historymentioning

confidence: 99%

Macromolecular Cryocrystallography

Garman¹,

Schneider²

1997

J Appl Cryst

338

289

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The current techniques for X-ray-diffraction data collection from macromolecular crystals at cryogenic temperatures are reviewed. The development of the experimental methods is outlined and the basic concepts pertaining to radiation damage and cryoprotection are summarized. Emphasis is placed on the practical aspects important to the success of the techniques, and a detailed account of these is presented.

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“…The type I enzymes are classified as either subfamily type IA if the protein links to the 5Ј phosphate or subfamily type IB when the protein attaches to the 3Ј phosphate. There is extensive sequence similarity among members of the same subfamily (10) but almost no sequence or structural similarity between the two subfamilies (11,12). All bacterial type I topoisomerases are type IA enzymes.…”

mentioning

confidence: 99%

New Alkaloid Antibiotics That Target the DNA Topoisomerase I of Streptococcus pneumoniae

Garcı́a

Blázquez

Ferrándiz

et al. 2011

Journal of Biological Chemistry

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Streptococcus pneumoniae has two type II DNA-topoisomerases (DNA-gyrase and DNA topoisomerase IV) and a single type I enzyme (DNA-topoisomerase I, TopA), as demonstrated here. Although fluoroquinolones target type II enzymes, antibiotics efficiently targeting TopA have not yet been reported. Eighteen alkaloids (seven aporphine and 11 phenanthrenes) were semisynthesized from boldine and used to test inhibition both of TopA activity and of cell growth. Two phenanthrenes (seconeolitsine and N-methyl-seconeolitsine) effectively inhibited both TopA activity and cell growth at equivalent concentrations (ϳ17 M). Evidence for in vivo TopA targeting by seconeolitsine was provided by the protection of growth inhibition in a S. pneumoniae culture in which the enzyme was overproduced. Additionally, hypernegative supercoiling was observed in an internal plasmid after drug treatment. Furthermore, a model of pneumococcal TopA was made based on the crystal structure of Escherichia coli TopA. Docking calculations indicated strong interactions of the alkaloids with the nucleotide-binding site in the closed protein conformation, which correlated with their inhibitory effect. Finally, although seconeolitsine and N-methyl-seconeolitsine inhibited TopA and bacterial growth, they did not affect human cell viability. Therefore, these new alkaloids can be envisaged as new therapeutic candidates for the treatment of S. pneumoniae infections resistant to other antibiotics.Antibiotic resistance in bacterial pathogens is a serious clinical problem. This problem affects Streptococcus pneumoniae (the pneumococcus), which, in addition to being one of the principal human pathogens, is the main ethyological agent of community-acquired pneumonia. Annually, approximately one million children aged Ͻ5 years die of pneumococcal pneumonia, meningitis, and/or sepsis worldwide (1). Resistance to currently used antimicrobial drugs for the treatment of pneumococcal infections, including ␤-lactams and macrolides, has spread worldwide in the last two decades (2). The new fluoroquinolones, such as levofloxacin and moxifloxacin, which act on type II DNA topoisomerases, are therapeutic alternatives for treatment of adult patients with community-acquired pneumonia (3). However, although resistance to fluoroquinolones in S. pneumoniae is still lower than 3% (4), an increase in resistance is likely to occur.DNA topoisomerases participate in almost all cellular functions involving DNA transactions (5). They solve the topological problems associated with DNA replication, transcription, and recombination. In addition, these enzymes fine-tune the steady-state level of DNA supercoiling, both facilitating protein interactions with the DNA and preventing excessive supercoiling that is deleterious. In bacteria, the homeostasis of DNA supercoiling is maintained by the opposing activities of topoisomerases that relax DNA and gyrase that introduces negative supercoils. The transcriptional response to DNA relaxation involves genes coding for all the DNA topoisomerases from S...

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Crystal structure of the amino-terminal fragment of vaccinia virus DNA topoisomerase I at 1.6 å resolution

Cited by 66 publications

References 38 publications

Computationally efficient molecular dynamics integrators with improved sampling accuracy

Computationally efficient molecular dynamics integrators with improved sampling accuracy

Macromolecular Cryocrystallography

New Alkaloid Antibiotics That Target the DNA Topoisomerase I of Streptococcus pneumoniae

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