The R. A. Evans - P. K. McElroy Award for 2009 best paper

Evans, Ralph A.

doi:10.1109/rams.2010.5448005

Cited by 6 publications

(8 citation statements)

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“…Crystals were then mounted on nylon loops and flash frozen at 77 K. X-ray diffraction data were collected at 100 K using beamline 7-1 at the Stanford Synchrotron Radiation Laboratory. Data were processed by MOSFLM and Scala, and molecular replacement was conducted with Molrep using the open form P450cam structure (PDB entries 3L61). Model fitting and refinement were conducted with Coot and Refmac5, respectively.…”

Section: Methodsmentioning

confidence: 99%

Effector Roles of Putidaredoxin on Cytochrome P450cam Conformational States

et al. 2016

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In this study, the effector role of Pdx (putidaredoxin) on cytochrome P450cam conformation is refined by attaching two different spin labels, MTSL or BSL (bifunctional spin-label) onto the F or G helices and using DEER (double electron-electron resonance) to measure the distance between labels. Recent EPR and crystallographic studies have observed that oxidized Pdx induces substrate-bound P450cam to change from the closed to the open state. However, this change was not observed by DEER in the reduced Pdx complex with carbon-monoxide-bound P450cam (Fe(2+)CO). In addition, recent NMR studies have failed to observe a change in P450cam conformation upon binding Pdx. Hence, resolving these issues is important for a full understanding the effector role of Pdx. Here we show that oxidized Pdx induces camphor-bound P450cam to shift from the closed to the open conformation when labeled on either the F or G helices with MTSL. BSL at these sites can either narrow the distance distribution widths dramatically or alter the extent of the conformational change. In addition, we report DEER spectra on a mixed oxidation state containing oxidized Pdx and ferrous CO-bound P450cam, showing that P450cam remains closed. This indicates that CO binding to the heme prevents P450cam from opening, overriding the influence exerted by Pdx binding. Finally, we report the open form P450cam crystal structure with substrate bound, which suggests that crystal packing effects may prevent conformational conversion. Using multiple labeling approaches, DEER provides a unique perspective to resolve how the conformation of P450cam depends on Pdx and ligand states.

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Section: Methodsmentioning

confidence: 99%

Effector Roles of Putidaredoxin on Cytochrome P450cam Conformational States

et al. 2016

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“…Diffraction data were collected at 120 K using an in-house diffractometer (Nonius FR 591) connected to 345 mm MarResearch image plate detector. The best crystal diffracted up to 1.65 Å resolution, and diffraction data were integrated and reduced using MOSFLM and scaled using SCALA from the CCP4 suite of programs . Crystal parameters and data collection statistics are summarized in Table .…”

Section: Methodsmentioning

confidence: 99%

Identification of 3,4-Dihydroisoquinoline-2(1H)-sulfonamides as Potent Carbonic Anhydrase Inhibitors: Synthesis, Biological Evaluation, and Enzyme−Ligand X-ray Studies

et al. 2010

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Following previous studies we herein report the exploration of the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects and enzyme selectivity of a small class of 1-(cyclo)alkylisoquinolines containing a sulfonamide function considered a key feature for inhibiting CA. The results of enzymatic assays against human (h) CA isoforms, hCA I and hCA II (cytosolic, ubiquitous enzymes), hCA IX (transmembrane, tumor-associated), and hCA XIV (transmembrane), suggested that the presence of C-1 small substituents on isoquinoline scaffold controls both inhibitory potency and selectivity. Some derivatives showed potent hCA IX and hCA XIV inhibitory effects at nanomolar concentrations as well as low affinity for the ubiquitous hCA II. Moreover, we report the X-ray crystal structure of one of these derivatives in complex with dominant human isoform II, thus confirming the sulfonamide--zinc interactions. Finally, the results of docking experiments suggested the hypothetic interactions in the catalytic binding site for the most active and selective hCA IX and hCA XIV inhibitor.

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“…Swift-XRT is an X-ray imaging spectrometer with an energy range of 0.3 to 10 keV (Burrows et al 2005). The XRT data are obtained using the Time-Sliced Spectra tool 3 (Evans et al 2009). The time intervals are chosen to overlap with the H.E.S.S.…”

Section: Swift-xrt Analysismentioning

confidence: 99%

“…In our analyses, we only include Photon Counting (PC) data. By using the data products from the Time-Sliced Spectra tool and selecting only the PC mode data, we avoid contamination from the dust rings (Tiengo et al 2022;Evans 2022).…”

Section: Swift-xrt Analysismentioning

confidence: 99%

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H.E.S.S. follow-up observations of GRB221009A

Collaboration¹,

Aharonian³

et al. 2023

Preprint

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GRB 221009A is the brightest gamma-ray burst ever detected. To probe the very-high-energy (VHE, >100 GeV) emission, the High Energy Stereoscopic System (H.E.S.S.) began observations 53 hours after the triggering event, when the brightness of the moonlight no longer precluded observations. We derive differential and integral upper limits using H.E.S.S. data from the third, fourth, and ninth nights after the initial GRB detection, after applying atmospheric corrections. The combined observations yield an integral energy flux upper limit of Φ 95% UL = 9.7 × 10 −12 erg cm −2 s −1 above E thr = 650 GeV. The constraints derived from the H.E.S.S. observations complement the available multiwavelength data. The radio to X-ray data are consistent with synchrotron emission from a single electron population, with the peak in the SED occurring above the X-ray band. Compared to the VHE-bright GRB 190829A, the upper limits for GRB 221009A imply a smaller gamma-ray to X-ray flux ratio in the afterglow. Even in the absence of a detection, the H.E.S.S. upper limits thus contribute to the multiwavelength picture of GRB 221009A, effectively ruling out an IC dominated scenario.

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The R. A. Evans - P. K. McElroy Award for 2009 best paper

Cited by 6 publications

References 0 publications

Effector Roles of Putidaredoxin on Cytochrome P450cam Conformational States

Effector Roles of Putidaredoxin on Cytochrome P450cam Conformational States

Identification of 3,4-Dihydroisoquinoline-2(1H)-sulfonamides as Potent Carbonic Anhydrase Inhibitors: Synthesis, Biological Evaluation, and Enzyme−Ligand X-ray Studies

H.E.S.S. follow-up observations of GRB221009A

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