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Joonghee Kim,
Kyuseok Kim,
Sungmin Hong,
Bojun Kwon,
Il Dong Yun,
Byung Se Choi,
Cheolkyu Jung, Jae Hyuk Lee,
You Hwan Jo,
Taeyun Kim,
Joong Eui Rhee,
Soo Hoon Lee
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ABSTRACT: OBJECTIVE: Recent studies suggested quantitative analysis of diffusion-weighted magnetic resonance imaging as a promising tool for early prognostication of cardiac arrest patients. However, most of their methods involve significant manual image handling often subjective and difficult to reproduce. Therefore developing a computerized analysis method using easy-to-define characteristics would be useful. METHODS: Comatose out-of-hospital cardiac arrest (OHCA) patients who underwent brain MRI between Jan, 2008 and July, 2012 were identified from an OHCA registry. Apparent diffusion coefficient (ADC) axial images were analyzed using a program to detect and characterize clusters of low ADC pixels from six brain regions including frontal, occipital, parietal, rolandic and temporal and basal ganglia region. Identified clusters were ranked according to size, mean ADC and minimum ADC to assess the regional maximum cluster size (MCS), lowest mean ADC (LMEAN) and lowest minimum ADC (LMIN). Their power to predict poor outcome, defined as 6-month CPC 3 or higher, was assessed by contingency table analyses. RESULTS: 51 OHCA patients were eligible during the study period. The sensitivities of MCS, LMEAN and LMIN to detect poor outcome varied according to brain region from 62.5 to 90.0%, 50.0 to 72.5% and 42.5 to 82.5% with their specificities set to 100%, respectively. The MCS of occipital region showed most favorable test profile (sensitivity 90%, specificity 100%; AUROC 0.940, 95% confidence interval 0.874 to 1.000) CONCLUSION: The cluster-based computerized image analysis might be a simple but useful method for prediction of poor neurologic outcome. Future studies validating its prognostic performance are required.
Resuscitation 04/2013; · 3.60 Impact Factor
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ABSTRACT: Trans-to-cis isomerization, the key reaction in photoactive proteins, usually cannot occur through the standard one-bond-flip mechanism. Owing to spatial constraints imposed by a protein environment, isomerization probably proceeds through a volume-conserving mechanism in which highly choreographed atomic motions are expected, the details of which have not yet been observed directly. Here we employ time-resolved X-ray crystallography to visualize structurally the isomerization of the p-coumaric acid chromophore in photoactive yellow protein with a time resolution of 100 ps and a spatial resolution of 1.6 Å. The structure of the earliest intermediate (I(T)) resembles a highly strained transition state in which the torsion angle is located halfway between the trans- and cis-isomers. The reaction trajectory of I(T) bifurcates into two structurally distinct cis intermediates via hula-twist and bicycle-pedal pathways. The bifurcating reaction pathways can be controlled by weakening the hydrogen bond between the chromophore and an adjacent residue through E46Q mutation, which switches off the bicycle-pedal pathway.
Nature Chemistry 03/2013; 5(3):212-20. · 20.52 Impact Factor
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Jae Hyuk Lee,
Michael Wulff,
Savo Bratos,
Jakob Petersen,
Laurent Guerin,
Jean-Claude Leicknam,
Marco Cammarata,
Qingyu Kong,
Jeongho Kim,
Klaus Braagaard Moller,
Hyotcherl Ihee
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ABSTRACT: Molecules are often born with high energy and large-amplitude vibrations. In solution, a newly formed molecule cools down by transferring energy to the surrounding solvent molecules. The progression of the molecular and solute−solvent cage structure during this fundamental process has been elusive,
and spectroscopic data generally do not provide such structural information. Here, we use picosecond X-ray liquidography (solution scattering) to visualize timedependent structural changes associated with the vibrational relaxation of I2 molecules in two different solvents, CCl4 and cyclohexane. The birth and vibrational relaxation of I2 molecules and the associated rearrangement of solvent molecules are mapped out in the form of a temporally varying interatomic distance distribution. The I−I distance increases up to ∼4 Å and returns to the equilibrium distance (2.67 Å) in the ground state, and the first solvation cage expands by ∼1.5 Å along the I−I axis and then shrinks back accompanying the structural change of the I2
molecule.
Journal of the American Chemical Society 02/2013; 135:3255-3261. · 9.91 Impact Factor
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ABSTRACT: This study revealed that CWR22Rv-1 cells overexpressing δ-catenin display bigger tumor formation and higher angiogenic potentials than their matched control cells in the CAM assay. In addition, δ-catenin overexpression in CWR22Rv-1 cells results in increased Hypoxia-Inducible Factor 1-alpha (HIF-1α and Vascular Endothelial Growth Factor (VEGF) expression. Furthermore, δ-catenin overexpression was found to enhance nuclear distribution of both β-catenin and HIF-1α in hypoxic condition, which is diminished by knockdown of δ-catenin. Our current study adds novel evidence regarding contribution of δ-catenin to the progression of prostate cancer.
FEBS letters 12/2012; · 3.54 Impact Factor
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ABSTRACT: OBJECTIVE: We sought to investigate the prognostic implication of early coagulopathy represented by initial DIC score in out-of-hospital cardiac arrest (OHCA). METHODS: OHCA registry was analyzed to identify patients with ROSC without recent use of anticoagulant between 2008 and 2011. Patients were assessed for prehosptial factors, initial laboratory results and therapeutic hypothermia. Outcome variables were survival discharge, 6-month CPC and survival duration within the first week after ROSC. Logistic regression and Cox proportional hazards models were used for both univariable and multivariable analysis. RESULTS: Among 273 eligible patients, initial DIC score was available in 252 (92.3%). Higher DIC score was associated with increased inhospital death (odds ratio [OR], 1.89 per unit; 95% confidence interval [CI], 1.48-2.41) and unfavorable long-term outcome (6-month CPC 3-5; OR, 2.21 per unit; 95% CI, 1.60-3.05). The adjusted ORs for both outcomes were 1.61 (95% CI, 1.17-2.22) and 1.84 (95% CI, 1.26-2.67), respectively. We categorized DIC score in five groups as <3, 3, 4, 5 and >5 and analyzed differential mortality risk using Cox proportional hazards model. Compared with reference group (DIC score<3), the adjusted HR for early mortality in each remaining group was 1.96 (95% CI, 1.13-3.40), 2.26 (95% CI, 1.27-4.02), 2.77 (95% CI, 1.58-4.85) and 4.29 (95% CI, 2.22-8.30), respectively (p-trend<0.001). The area under the receiver operating characteristic of DIC score for prediction of unfavorable long-term outcome was 0.79 (95% CI, 0.69-0.88). CONCLUSION: Increased initial DIC score in OHCA was an independent predictor for poor outcomes and early mortality risk.
Resuscitation 09/2012; · 3.60 Impact Factor
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ABSTRACT: BACKGROUND: MRI-based prognostication of comatose cardiac arrest survivors has shown promising results. However, the technique has not been validated in patients treated with therapeutic hypothermia and it is unknown how it might add to NSE-based prognostication. We sought to evaluate the prognostic performance of regional apparent diffusion coefficient (ADC) in comatose out-of-hospital cardiac arrest (OHCA) patients treated with mild hypothermia and its added value to NSE-based prognostication. METHODS: An OHCA registry was analyzed to identify OHCA patients older than 15 who were treated with therapeutic hypothermia and underwent brain MRI between 2008 and 2011. Quantitative measurement of regional ADCs was performed by a radiologist blinded to the clinical outcome. RESULTS: Of the 43 eligible patients, 11 (18.6 %) achieved a good outcome (6-month CPC of 1 or 2). The regional ADC of the occipital cortex showed the highest discriminatory power with an area under the curve of receiver operating characteristic (AUROC) of 0.943 (95 % CI, 0.872-1.000) and predicted poor outcomes with a sensitivity of 90.6 % and a specificity of 100 %. The AUROC for NSE levels (48-h) was 0.911 (95 % CI, 0.801-1.000) which was significantly correlated with the regional ADC (Pearson's r = -0.674, p < .001). The ADC-based predictions identified an additional 5 (35.7 %) poor outcome patients out of 14 with 48-h NSE levels less than 78.9 ng/mL, which is the cutoff point suggested in a previous study. However, additional prognostic information was not provided when the 48-h NSE levels were >78.9 ng/mL. CONCLUSIONS: Regional ADC-based prognostication was accurate in OHCA patients who were treated with mild hypothermia. However, it only provided additional prognostic information when the 48-h NSE levels indicated a good prognosis (48-h NSE <78.9 ng/mL).
Neurocritical Care 08/2012; · 2.47 Impact Factor
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ABSTRACT: BACKGROUND: Red cell distribution width (RDW) is associated with mortality in both the general population and in patients with certain diseases. However, the relationship between RDW and mortality in patients with community-acquired pneumonia (CAP) is unknown. The objective of this study was to evaluate the association of RDW with mortality in patients with CAP. METHODS: We performed a retrospective analysis of a prospective registry database of patients with CAP. Red cell distribution width was organized into quartiles. The pneumonia severity index (PSI) and CURB-65 were calculated. The primary outcome was 30-day mortality. Secondary outcomes included the length of hospital stay, admission to the intensive care unit, vasopressor use, and the need for mechanical ventilation. RESULTS: A total of 744 patients were included. The PSI and CURB-65 were higher in patients with a high RDW. Multivariate logistic regression analysis identified higher categories of RDW, PSI, CURB-65, and albumin as statistically significant variables. Thirty-day mortality was significantly higher in patients with a higher RDW. Among the secondary outcomes, the length of hospital stay and vasopressor use were significantly different between the groups. In a Cox proportional hazard regression analysis, patients with higher categories of RDW exhibited increased mortality before and after adjustment of the severity scales. Receiver operating characteristics curves demonstrated improved mortality prediction when RDW was added to the PSI or CURB-65. CONCLUSION: Red cell distribution width was associated with 30-day mortality, length of hospital stay, and use of vasopressors in hospitalized patients with CAP. The inclusion of RDW improved the prognostic performance of the PSI and CURB-65.
The American journal of emergency medicine 08/2012; · 1.54 Impact Factor
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Hangun Kim,
Yongfeng He,
Ilhwan Yang,
Yan Zeng,
Yonghee Kim,
Young-Woo Seo,
Mary Jo Murnane,
Chaeyong Jung, Jae-Hyuk Lee,
Jeong-Joon Min,
Dong-Deuk Kwon,
Kyung Keun Kim,
Qun Lu,
Kwonseop Kim
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ABSTRACT: δ-Catenin binds the juxtamembrane domain of E-cadherin and is known to be overexpressed in some human tumors. However, the functions of δ-catenin in epithelial cells and carcinomas remain elusive. We found that prostate cancer cells overexpressing δ-catenin show an increase in multi-layer growth in culture. In these cells, δ-catenin colocalizes with E-cadherin at the plasma membrane, and the E-cadherin processing is noticeably elevated. E-Cadherin processing induced by δ-catenin is serum-dependent and requires MMP- and PS-1/γ-secretase-mediated activities. A deletion mutant of δ-catenin that deprives the ability of δ-catenin to bind E-cadherin or to recruit PS-1 to E-cadherin totally abolishes the δ-catenin-induced E-cadherin processing and the multi-layer growth of the cells. In addition, prostate cancer cells overexpressing δ-catenin display an elevated total β-catenin level and increase its nuclear distribution, resulting in the activation of β-catenin/LEF-1-mediated transcription and their downstream target genes as well as androgen receptor-mediated transcription. Indeed, human prostate tumor xenograft in nude mice, which is derived from cells overexpressing δ-catenin, shows increased β-catenin nuclear localization and more rapid growth rates. Moreover, the metastatic xenograft tumor weights positively correlate with the level of 29kD E-cadherin fragment, and primary human prostate tumor tissues also show elevated levels of δ-catenin expression and the E-cadherin processing. Taken together, these results suggest that δ-catenin plays an important role in prostate cancer progression through inducing E-cadherin processing and thereby activating β-catenin-mediated oncogenic signals.
Biochimica et Biophysica Acta 04/2012; 1822(4):509-21. · 4.66 Impact Factor
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ABSTRACT: Although emergency department (ED) crowding has been shown to be associated with delayed antibiotics treatment in community-acquired pneumonia (CAP) patients, association between ED crowding with mortality has not been investigated. We hypothesized emergency department crowding is associated with 28-day mortality in CAP patients.
A retrospective observational study using prospective database was performed on CAP patients who visited a single, urban, tertiary care hospital ED between April 1, 2008 and September 30, 2009. Main outcomes were 28-day mortality and timeliness of antibiotic therapy (within 2, 4, 6, and 8 h of arrival). ED crowding was measured by Emergency Department Occupancy (EDO) rate. A multivariate logistic regression was performed to determine the association of 28-day mortality with EDO rate after adjusting for factors such as time-to-first-antibiotic-dose (TFAD), pneumonia severity index and laboratory markers.
477 cases were enrolled during the study period. 28-day mortality rate was 4.8%. EDO rate ranged from 37.2% to 162.8%, and median was 97.7% (IQR: 80.2%-116.3%). When categorized into tertiles by EDO rate, high crowding condition (EDO rate >109.3%) was significantly associated with a higher 28-day mortality (adjusted OR = 9.48, 95% CI 1.53-58.90). However, TFAD was not associated with 28-day mortality. ED crowding was not associated with delay of TFAD at various time intervals (2, 4, 6, and 8 h).
ED crowding measured by EDO rate was associated with higher 28-day mortality in CAP patients after adjusting TFAD, pneumonia severity index (PSI), and laboratory markers, although there was no association between ED crowding and TFAD.
The Journal of infection 03/2012; 64(3):268-75. · 4.13 Impact Factor
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Tae Wu Kim, Jae Hyuk Lee,
Jungkweon Choi,
Kyung Hwan Kim,
Luuk J van Wilderen,
Laurent Guerin,
Youngmin Kim,
Yang Ouk Jung,
Cheolhee Yang,
Jeongho Kim,
Michael Wulff,
Jasper J van Thor,
Hyotcherl Ihee
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ABSTRACT: Photoreceptor proteins play crucial roles in receiving light stimuli that give rise to the responses required for biological function. However, structural characterization of conformational transition of the photoreceptors has been elusive in their native aqueous environment, even for a prototype photoreceptor, photoactive yellow protein (PYP). We employ pump-probe X-ray solution scattering to probe the structural changes that occur during the photocycle of PYP in a wide time range from 3.16 μs to 300 ms. By the analysis of both kinetics and structures of the intermediates, the structural progression of the protein in the solution phase is vividly visualized. We identify four structurally distinct intermediates and their associated five time constants and reconstructed the molecular shapes of the four intermediates from time-independent, species-associated difference scattering curves. The reconstructed structures of the intermediates show the large conformational changes such as the protrusion of N-terminus, which is restricted in the crystalline phase due to the crystal contact and thus could not be clearly observed by X-ray crystallography. The protrusion of the N-terminus and the protein volume gradually increase with the progress of the photocycle and becomes maximal in the final intermediate, which is proposed to be the signaling state. The data not only reveal that a common kinetic mechanism is applicable to both the crystalline and the solution phases, but also provide direct evidence for how the sample environment influences structural dynamics and the reaction rates of the PYP photocycle.
Journal of the American Chemical Society 02/2012; 134(6):3145-53. · 9.91 Impact Factor
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ABSTRACT: Post-resuscitation period is characterized by high early mortality due to post-cardiac arrest syndrome. Recent studies found that elevated red cell distribution width (RDW) is a strong predictor of mortality in critically ill patients. We investigated the prognostic significance of RDW in out-of-hospital cardiac arrest (OHCA) victims.
Analysis of emergency department OHCA registry extending from January 2007 to December 2010 was conducted. Patients with ROSC were assessed for Utstein predictors including sex, age, arrest location, presence of witness, bystander cardiopulmonary resuscitation, response time, initial rhythm and cause of arrest. RDW, hematocrit, white blood cell and platelet counts, blood urea nitrogen (BUN), creatinine and albumin were also obtained. Outcome variable was survival duration within 30 days. RDW was categorized in quartiles as <13.2%, 13.2% to 14.0%, 14.1% to 15.4% and >15.4%. Hazard ratios (HRs) were estimated using Cox-proportional hazard models in both univariate and multivariate analysis. All prognostic variables with their p value<0.1 in univariate analysis were used in multivariate analysis for adjustment.
Among 409 OHCA patients, 219 patients had ROSC. Highest RDW quartile (RDW>15.4%), female sex, older age, non-shockable initial rhythm, increased BUN and creatinine and decreased albumin, hematocrit and platelet count were associated with increased mortality in univariate analysis. In multivariate analysis, the highest RDW quartile was independently associated with all-cause mortality (HR=1.95; 95% CI 1.05-3.60; p=0.034) during 30-day post-resuscitation period. Other significant variables were age, initial rhythm and serum albumin.
Initial RDW is an independent predictor of all-cause mortality in post-resuscitation patients.
Resuscitation 02/2012; 83(10):1248-52. · 3.60 Impact Factor
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Tae Wu Kim†, Jae Hyuk Lee†,
Jungkweon Choi†,
Kyung Hwan Kim†,
Luuk J. van Wilderen‡,
Laurent Guerin§,
Youngmin Kim†,
Yang Ouk Jung†,
Cheolhee Yang†,
Jeongho Kim†,
Michael Wulff§,
Jasper J. van Thor*‡,
Hyotcherl Ihee*†
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[hide abstract]
ABSTRACT: Photoreceptor proteins play crucial roles in receiving light stimuli that give rise to the responses required for biological function. However, structural characterization of conformational transition of the photoreceptors has been elusive in their native aqueous environment, even for a prototype photoreceptor, photoactive yellow protein (PYP). We employ pump–probe X-ray solution scattering to probe the structural changes that occur during the photocycle of PYP in a wide time range from 3.16 μs to 300 ms. By the analysis of both kinetics and structures of the intermediates, the structural progression of the protein in the solution phase is vividly visualized. We identify four structurally distinct intermediates and their associated five time constants and reconstructed the molecular shapes of the four intermediates from time-independent, species-associated difference scattering curves. The reconstructed structures of the intermediates show the large conformational changes such as the protrusion of N-terminus, which is restricted in the crystalline phase due to the crystal contact and thus could not be clearly observed by X-ray crystallography. The protrusion of the N-terminus and the protein volume gradually increase with the progress of the photocycle and becomes maximal in the final intermediate, which is proposed to be the signaling state. The data not only reveal that a common kinetic mechanism is applicable to both the crystalline and the solution phases, but also provide direct evidence for how the sample environment influences structural dynamics and the reaction rates of the PYP photocycle.
Journal of American Chemical Society. 01/2012;
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Tae Wu Kim, Jae Hyuk Lee,
Jungkweon Choi,
Kyung Hwan Kim,
Luuk J. van Wilderen,
Laurent Guerin,
Youngmin Kim,
Yang Ouk Jung,
Cheolhee Yang,
Jeongho Kim,
Michael Wulff,
Jasper J. van Thor,
Hyotcherl Ihee
[show abstract]
[hide abstract]
ABSTRACT: Photoreceptor proteins play crucial roles in receiving light stimuli that give rise to the responses required for biological function. However, structural characterization of conformational transition of the photoreceptors has been elusive in their native aqueous environment, even for a prototype photoreceptor, photoactive yellow protein (PYP). We employ pump-probe X-ray solution scattering to probe the structural changes that occur during the photocycle of PYP in a wide time range from 3.16 μs to 300 ms. By the analysis of both kinetics and structures of the intermediates, the structural progression of the protein in the solution phase is vividly visualized. We identify four structurally distinct intermediates and their associated five time constants and reconstructed the molecular shapes of the four intermediates from time-independent, species-associated difference scattering curves. The reconstructed structures of the intermediates show the large conformational changes such as the protrusion of N-terminus, which is restricted in the crystalline phase due to the crystal contact and thus could not be clearly observed by X-ray crystallography. The protrusion of the N-terminus and the protein volume gradually increase with the progress of the photocycle and becomes maximal in the final intermediate, which is proposed to be the signalling state. The data not only reveal that a common kinetic mechanism is applicable to both the crystalline and solution phases, but also provide direct evidence for how the sample environment influences structural dynamics and the reaction rates of the PYP photocycle.
Journal of the American Chemical Society 01/2012; 134(6):3145-3153. · 9.91 Impact Factor
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ABSTRACT: Malignant gastrointestinal stromal tumors (GISTs) are rare non-epithelial, mesenchymal neoplasms of the gastrointestinal tract that metastasize or recur in 30% of patients who undergo surgical resection with curative intent. A 59-year-old man visited our hospital for an examination of a palpable mass in the left abdomen. Fourteen months prior to his visit, the patient underwent gastric wedge resection to remove a GIST of the gastric cardia. At the time of surgery, no evidence of metastatic disease was observed and the pathological interpretation was a high-risk GIST. A follow-up computed tomography scan of the abdomen revealed a partially necrotic solid mass (9.8 × 7.6 cm) and enhancing mass in the spleen (2.3 cm). On exploration, multiple masses were found in the liver, greater omentum, and mesentery. Here, we report a case of recurring GIST of the stomach that metastasized to the spleen. To the best of our knowledge, few reports of metastasis to the spleen exist.
Journal of the Korean Surgical Society. 12/2011; 81 Suppl 1:S25-9.
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Young Hoe Hur,
Ho Hyun Kim,
Eun Kyu Park,
Jin Shick Seoung,
Jin Woong Kim,
Yong Yeon Jeong, Jae Hyuk Lee,
Yang Seok Koh,
Jung Chul Kim,
Hyun Jong Kim,
Chol Kyoon Cho
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ABSTRACT: Primary sarcomas of the pancreas are extremely rare, accounting for 0.1% of malignant pancreatic (non-islet) neoplasms. Pancreatic leiomyosarcoma is a highly aggressive malignancy that spreads in a similar manner to gastric leiomyosarcoma, i.e., by adjacent organ invasion, hematogenous spread, and lymph node metastasis. These tumors are large at the time of diagnosis and are usually found at an advanced stage. We report a case of a 70-year-old female with intermittent right upper quadrant abdominal discomfort. Radiological, histopathological, and immunohistochemical studies revealed the tumor to be a primary leiomyosarcoma of the pancreas. Herein, we describe a patient with a primary leiomyosarcoma of the pancreas who presented with clinical and radiological findings indicative of a mass in the pancreatic head.
Journal of the Korean Surgical Society. 12/2011; 81 Suppl 1:S69-73.
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ABSTRACT: We investigate the structural dynamics of iodine elimination reaction of 1,2-diiodoethane (C(2)H(4)I(2)) in cyclohexane by applying time-resolved X-ray liquidography (TRXL). The TRXL technique combines structural sensitivity of X-ray diffraction and 100 ps time resolution of X-ray pulses from synchrotron and allows direct probing of transient structure of reacting molecules. From the analysis of time-dependent X-ray solution scattering patterns using global fitting based on DFT calculation and MD simulation, we elucidate the kinetics and structure of transient intermediates resulting from photodissociation of C(2)H(4)I(2). In particular, the effect of solvent on the reaction kinetics and pathways is examined by comparison with an earlier TRXL study on the same reaction in methanol. In cyclohexane, the C(2)H(4)I radical intermediate undergoes two branched reaction pathways, formation of C(2)H(4)I-I isomer and direct dissociation into C(2)H(4) and I, while only isomer formation occurs in methanol. Also, the C(2)H(4)I-I isomer has a shorter lifetime in cyclohexane by an order of magnitude than in methanol. The difference in the reaction dynamics in the two solvents is accounted for by the difference in solvent polarity. In addition, we determine that the C(2)H(4)I radical has a bridged structure, not a classical structure, in cyclohexane.
The Journal of Physical Chemistry A 11/2011; 116(11):2713-22. · 2.95 Impact Factor
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ABSTRACT: The signaling state of the photoactive yellow protein (PYP) photoreceptor is transiently developed via isomerization of its blue-light-absorbing chromophore. The associated structural rearrangements have large amplitude but, due to its transient nature and chemical exchange reactions that complicate NMR detection, its accurate three-dimensional structure in solution has been elusive. Here we report on direct structural observation of the transient signaling state by combining double electron electron resonance spectroscopy (DEER), NMR, and time-resolved pump-probe X-ray solution scattering (TR-SAXS/WAXS). Measurement of distance distributions for doubly spin-labeled photoreceptor constructs using DEER spectroscopy suggests that the signaling state is well ordered and shows that interspin-label distances change reversibly up to 19 Å upon illumination. The SAXS/WAXS difference signal for the signaling state relative to the ground state indicates the transient formation of an ordered and rearranged conformation, which has an increased radius of gyration, an increased maximum dimension, and a reduced excluded volume. Dynamical annealing calculations using the DEER derived long-range distance restraints in combination with short-range distance information from (1)H-(15)N HSQC perturbation spectroscopy give strong indication for a rearrangement that places part of the N-terminal domain in contact with the exposed chromophore binding cleft while the terminal residues extend away from the core. Time-resolved global structural information from pump-probe TR-SAXS/WAXS data supports this conformation and allows subsequent structural refinement that includes the combined energy terms from DEER, NMR, and SAXS/WAXS together. The resulting ensemble simultaneously satisfies all restraints, and the inclusion of TR-SAXS/WAXS effectively reduces the uncertainty arising from the possible spin-label orientations. The observations are essentially compatible with reduced folding of the I(2)' state (also referred to as the 'pB' state) that is widely reported, but indicates it to be relatively ordered and rearranged. Furthermore, there is direct evidence for the repositioning of the N-terminal region in the I(2)' state, which is structurally modeled by dynamical annealing and refinement calculations.
Journal of the American Chemical Society 06/2011; 133(24):9395-404. · 9.91 Impact Factor
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ABSTRACT: Here we report structural dynamics of equine myoglobin (Mb) in response to the CO photodissociation visualized by picosecond time-resolved X-ray solution scattering. The data clearly reveal new structural dynamics that occur in the timescale of ∼360 picoseconds (ps) and ∼9 nanoseconds (ns), which have not been clearly detected in previous studies.
Chemical Communications 01/2011; 47(1):289-91. · 6.17 Impact Factor
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ABSTRACT: We investigate the photoinduced dissociation of HgBr(2) in methanol and the ensuring structural dynamics of the photo-products over a time span from 100 ps to 1 μs after photolysis at 267 nm by using time-resolved X-ray liquidography (TRXL). By making use of the atomic-level structural sensitivity of X-ray scattering and the superb 100 ps time resolution of X-ray pulses from a 3rd-generation synchrotron, the structural dynamics of a chemical reaction in solution can be directly monitored. The measured time-dependent X-ray solution scattering signals, analyzed using global-fitting based on DFT calculations and MD simulations, show that photoexcited HgBr(2) dissociates via both two-body (HgBr + Br) and three-body (Hg + Br + Br) dissociation pathways with a ∼2 : 1 branching ratio. Following dissociation, the photoproducts recombine via three reactions involving Br species: (1) Hg + Br, (2) HgBr + Br, and (3) Br + Br. The associated rate constants and branching ratios are determined from the global-fitting analysis. Also, we examine the energy dissipation from reacting solute molecules and relaxation of excited molecules to solvent bath accompanying the temperature rise of 0.54 K. Compared to a previous TRXL study of the photodissociation of HgI(2), the results of this work suggest that the photodissociation pathway of HgBr(2) is different from that of HgI(2), which dissociates predominantly via two-body dissociation, at least to within the currently available time resolution of ∼100 ps. In addition, the error analysis of the fit parameters used in the global-fitting are discussed in detail with a comparison of various error estimation algorithms.
Physical Chemistry Chemical Physics 10/2010; 12(37):11536-47. · 3.57 Impact Factor
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ChemPhysChem 10/2010; 11(14):3034. · 3.41 Impact Factor
