Verification of protein structures: Patterns of nonbonded atomic interactions

Colovos, Christos; Yeates, T.O.

doi:10.1002/pro.5560020916

Cited by 3,520 publications

(2,153 citation statements)

References 26 publications

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“…Accordingly, ligands were then transferred among target structures, keeping their orientation as a restraint for the subsequent modelling process. Subsequently, models were selected on the basis of high molpdf score and subjected to loop refinement and model validation using iterative evaluation of Ramachandran plot, ERRAT plot and ProSA Z-core (Colovos and Yeates, 1993;Lovell et al, 2003;Wiederstein and Sippl, 2007).…”

Section: Homology Modellingmentioning

confidence: 99%

In vitro and In vivo antimycobacterial, hepatoprotective and immunomodulatory activity of Euclea natalensis and its mode of action

Lall

Kumar

Meyer

et al. 2016

Journal of Ethnopharmacology

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Ethnopharmacological relevance: The Natal gwarri or Natal ebony (Euclea natalensis A.DC.) is a deciduous tree found widespread throughout southern Africa, especially in Kwazulu-Natal and the southern cost. It has been widely used by indigenous communities such as the Zulus, Tsongas and Vendas for symptoms related to tuberculosis (TB). The decoctions made from the plant parts are administered for chest diseases to treat complications such as chest pains, bronchitis, pleurisy and asthma. TB is prevalent in immune-compromised patients and it is evident that TB-drugs cause hepatotoxicity. The objective of the present study was therefore to evaluate the antimycobacterial activity of the 2 ethanolic extract of E. natalensis against TB and its hepatoprotective and immunomodulatory activities. Materials and methods:The antimycobacterial, antioxidant, hepatoprotective, immunomodulatory activity and cytotoxicity of the ethanolic extract of the shoots of E. natalensis were determined in vitro. The mechanism of action of the antituberculosis activity was determined by investigating the inhibitory effect on mycothiol disulfide reductase enzyme. Furthermore, the acute, sub-acute toxicity (50-2000 mg/kg) and antimycobacterial effect (300 mg/kg) of E. natalensis shoot extract were investigated in Balb/c mice.Hepatoprotective activity of the extract (50-150 mg/kg) was evaluated on isoniazid and rifampicin (50 mg/kg; i.p.) induced hepatic damage in a rat model. Results:The minimum inhibitory concentration of the extract was found to be 125 µg/ml against Mycobacterium tuberculosis. The extracts fifty percent inhibitory concentration (IC 50 ) against 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical was found to be 22.55 µg/ml. The plant showed a hepatoprotective effect (50% at 12.5 µg/ml) and the ability to increase Thelper 1 cell cytokines; Interleukin 12, Interleukin 2 and Interferon α by up to 12 fold and the ability to decrease the T-helper 2 cell cytokine Interleukin 10 4 fold when compared to baseline cytokine production. No cellular toxicity was observed in primary peripheral blood mononuclear cells (PBMC's) and two secondary cell lines; U937 monocytes and Chang liver cells (a derivative of the HepG2 cell line). During mechanistic studies, the extract showed a 50% inhibition of mycothiol reductase activity at 38.62 µg/ml. During the acute and subacute studies, E. natalensis exhibited no toxic effect and the fifty percent lethal dose (LD 50 ) was established to be above 2000 mg/kg. The extract was able to reduce the mycobacterial load (1.5-fold reduction) in infected mice. Isoniazid and rifampicin caused significant hepatic damage in rats, and the extract was able to reduce the toxicity by 15% and 40% at 50 and 150 mg/kg respectively. Conclusion:The present study supports the traditional usage of the plant against tuberculosis symptoms. The study showed the ability of E. natalensis shoot extract to inhibit mycobacterial growth, stimulate an appropriate immune response and have a hepatic protective effect. Due to the ...

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Section: Homology Modellingmentioning

confidence: 99%

In vitro and In vivo antimycobacterial, hepatoprotective and immunomodulatory activity of Euclea natalensis and its mode of action

Lall

Kumar

Meyer

et al. 2016

Journal of Ethnopharmacology

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“…42 Simulated annealing was performed in PHENIX. 43 The structure was validated using the programs PRO-CHECK (version 3.5.4), 44 ERRAT, 45 and VERI-FY_3D. 46 Although addition of NAD to the crystallization solution improved the size and quality of the crystals, no clear electron density was observed for NAD.…”

Section: Esi Mass Spectrometrymentioning

confidence: 99%

Structure of the dimerization domain of DiGeorge Critical Region 8

et al. 2010

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Maturation of microRNAs (miRNAs,~22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298-352) at 1.7 Å resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis.

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“…The final model was assessed using the following structure assessment programs: Verify3D, ERRAT [30], PROCHECK [31], QMEAN [32]. …”

Section: Generation Of a 3d Model Of Cyp2j2mentioning

confidence: 99%

Computational modelling of the binding of arachidonic acid to the human monooxygenase CYP2J2

et al. 2016

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Verification of protein structures: Patterns of nonbonded atomic interactions

Cited by 3,520 publications

References 26 publications

In vitro and In vivo antimycobacterial, hepatoprotective and immunomodulatory activity of Euclea natalensis and its mode of action

In vitro and In vivo antimycobacterial, hepatoprotective and immunomodulatory activity of Euclea natalensis and its mode of action

Structure of the dimerization domain of DiGeorge Critical Region 8

Computational modelling of the binding of arachidonic acid to the human monooxygenase CYP2J2

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