Dataset Information

Analyzing In Silico the Relationship Between the Activation of the Edema Factor and Its Interaction With Calmodulin.

ABSTRACT: Molecular dynamics (MD) simulations have been recorded on the complex between the edema factor (EF) of Bacilllus anthracis and calmodulin (CaM), starting from a structure with the orthosteric inhibitor adefovir bound in the EF catalytic site. The starting structure has been destabilized by alternately suppressing different co-factors, such as adefovir ligand or ions, revealing several long-distance correlations between the conformation of CaM, the geometry of the CaM/EF interface, the enzymatic site and the overall organization of the complex. An allosteric communication between CaM/EF interface and the EF catalytic site, highlighted by these correlations, was confirmed by several bioinformatics approaches from the literature. A network of hydrogen bonds and stacking interactions extending from the helix V of of CaM, and the residues of the switches A, B and C, and connecting to catalytic site residues, is a plausible candidate for the mediation of allosteric communication. The greatest variability in volume between the different MD conditions was also found for cavities present at the EF/CaM interface and in the EF catalytic site. The similarity between the predictions from literature and the volume variability might introduce the volume variability as new descriptor of allostery.

SUBMITTER: Pitard I

PROVIDER: S-EPMC7746812 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Analyzing <i>In Silico</i> the Relationship Between the Activation of the Edema Factor and Its Interaction With Calmodulin.

Pitard Irène I Monet Damien D Goossens Pierre L PL Blondel Arnaud A Malliavin Thérèse E TE

Frontiers in molecular biosciences 20201204

Molecular dynamics (MD) simulations have been recorded on the complex between the edema factor (EF) of <i>Bacilllus anthracis</i> and calmodulin (CaM), starting from a structure with the orthosteric inhibitor adefovir bound in the EF catalytic site. The starting structure has been destabilized by alternately suppressing different co-factors, such as adefovir ligand or ions, revealing several long-distance correlations between the conformation of CaM, the geometry of the CaM/EF interface, the enz ...[more]

PMID: 33344505

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Project description:PURPOSE:To investigate the relationship between diabetic macular edema (DME) and the choroidal layer thickness in diabetic patients. METHODS:This is a retrospective observation study. Three hundred eighteen eyes of 159 diabetes mellitus (DM) patients and age-matched 100 eyes of 79 healthy controls were enrolled. DME was defined as over 300 ?m in the central retinal subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid sector. The central choroidal thickness (CCT), as well as inner and outer layers were determined based on enhanced depth imaging (EDI)-OCT. Diabetic patients with/without systemic diabetic treatments (DT) at the start of this study was defined as DT+ and DT-, respectively. The number of eyes examined was 62 and 256 eyes in DME+and DME-groups, respectively. DM patients were further subdivided into 4 groups with/without DME and DT; DME+DT+(35 eyes), DME-DT+(159 eyes), DME+DT-(27 eyes), and DME-DT-group (97 eyes). Multiple comparisons on CCT layers including control and each DM group were statistically examined. RESULTS:The total CCT layer was 254±83, 283±88, and 251±70 ?m in the control, DME+, and DME-group, respectively. A total CCT layer in DME+was significantly thicker than the DME-group (P < 0.05). The outer CCT layer was 195±75, 222±83, and 193±63 ?m in the control, DME+, and DME-group, respectively. The outer CCT layer in DME+ was significantly thicker than the DME-group (P < 0.05). In the subdivided groups, the total CCT layers in the control, DME+DT+, DME-DT+, DME+DT-and DME-DT-groups were 254±83, 274±88, 247±66, 290±84 and 258±75 ?m, respectively. The outer CCT layers in each group were 195±75, 214±83, 189±58, 228±77, and 201±70 ?m, respectively. Total CCT and the outer layer in DME+DT-was significantly thicker than the DME-DT+group (each P < 0.05). In contrast, there was no significant difference in inner layer between the groups. CONCLUSIONS:The total and outer CCT layers of diabetic eyes were significantly thickened in the DME+DT-as compared with the DME-DT+group, suggesting that CCT may be related to the pathology of DME.

Project description:PurposeTo assess whether aqueous flare is related to an increased risk of pseudophakic cystoid macular edema (PCME) following uneventful cataract surgery in nondiabetic and diabetic patients.MethodsA post hoc analysis of five consecutive randomized clinical trials in the Department of Ophthalmology, Kymenlaakso Central Hospital, Finland. Aqueous flare levels were recorded in 448 eyes of 448 patients before surgery, and after the course of topical anti-inflammatory treatment 28 days and three months after cataract surgery.ResultsAqueous flare increase of <50%, ≥50%, ≥100%, and ≥200% associated in central subfield macular thickness (CSMT) increase across the groups at 28 days and three months after surgery. Increase of aqueous flare ≥100% compared to those with <100% was associated with increased CSMT (P = 0.022 at 28 days, and P = 0.027 at three months). At three months, macular thickening (at least 10% CSMT increase) was observed in 12.7% compared to 4.6% of eyes when using a cutoff value of 100% increase in aqueous flare (P = 0.033). Although diabetic patients presented higher aqueous flare levels at baseline compared to nondiabetic patients (12.9 ± 11.8 vs. 9.8 ± 8.2 photon units/ms P < 0.001), the postoperative levels illustrated a similar profile in aqueous flare increase between the two groups.ConclusionsAt 28 days, aqueous flare increase was associated with macular thickening. A 100% cutoff value could potentially be used when studying anti-inflammatory efficacy of different treatment protocols. Flare values exceeding this cutoff value could be considered as an indication for extending anti-inflammatory therapy.Translational relevanceA 100% increase in aqueous flare at 28 days after cataract surgery from baseline predicted macular thickening up to three months postoperatively. Identifying a correlation between increased aqueous flare levels and pseudophakic cystoid macular edema may allow recognition of the most vulnerable patients, development of prophylactic treatment strategies and reduction of the number and severity of postoperative complications.

Dataset Information

Analyzing In Silico the Relationship Between the Activation of the Edema Factor and Its Interaction With Calmodulin.

Publications

Analyzing <i>In Silico</i> the Relationship Between the Activation of the Edema Factor and Its Interaction With Calmodulin.

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