The RCSB PDB information portal for structural genomics

Kouranov, Andrei; Xie, Lei; Cruz, Joanna de la; Chen, Li; Westbrook, John D.; Bourne, Philip E.; Berman, Helen M.

doi:10.1093/nar/gkj120

Cited by 369 publications

(276 citation statements)

References 15 publications

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“…Immunoblot bands were acquired using an Epson Perfection 4870 Photo instrument (Epson, Long Beach, CA), and selected bands were quantified based on their relative intensities using ImageJ densitometry software (version 1.6; National Institutes of Health, Bethesda, MD). (30). Both structures were submitted to the Patchdock and GRAMMX protein-protein docking servers without including Mg ions for rigid, blind docking (54,59).…”

Section: Methodsmentioning

confidence: 99%

Ebolavirus Proteins Suppress the Effects of Small Interfering RNA by Direct Interaction with the Mammalian RNA Interference Pathway

Fabozzi¹,

Nabel²,

Dolan

et al. 2011

J Virol

126

104

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Cellular RNA interference (RNAi) provides a natural response against viral infection, but some viruses have evolved mechanisms to antagonize this form of antiviral immunity. To determine whether Ebolavirus (EBOV) counters RNAi by encoding suppressors of RNA silencing (SRSs), we screened all EBOV proteins using an RNAi assay initiated by exogenously delivered small interfering RNAs (siRNAs) against either an EBOV or a reporter gene. In addition to viral protein 35 (VP35), we found that VP30 and VP40 independently act as SRSs. Here, we present the molecular mechanisms of VP30 and VP35. VP30 interacts with Dicer independently of siRNA and with one Dicer partner, TRBP, only in the presence of siRNA. VP35 directly interacts with Dicer partners TRBP and PACT in an siRNA-independent fashion and in the absence of effects on interferon (IFN). Taken together, our findings elucidate a new mechanism of RNAi suppression that extends beyond the role of SRSs in double-stranded RNA (dsRNA) binding and IFN antagonism. The presence of three suppressors highlights the relevance of host RNAi-dependent antiviral immunity in EBOV infection and illustrates the importance of RNAi in shaping the evolution of RNA viruses.RNA interference (RNAi) is a sequence-specific gene regulatory pathway widely conserved from plants to mammals (16, 47) that provides a natural cellular response to viral infection. Since mammals have evolved complex protein-based adaptive and innate immunity in response to infection, the existence of a nucleic acid-based innate immunity such as RNAi was initially debated. To date, several studies have provided experimental support to clarify the role of RNAi-based immunity in mammals. The identification of proteins working as suppressors of RNAi in animal virus (38) and of noncoding adenoviral RNAs able to inhibit components of the RNAi machinery (64) as well the presence of virus-derived small RNAs (3,11,48) and the observation that engineered RNAi can successfully restrict viral infection in mammalian cells (4,17,18,28,31) support a role for RNAi as an innate antiviral mechanism (3,11,38,48).The first mechanistic step of the RNAi pathway involves Dicer, an RNase III-type enzyme that processes doublestranded RNAs (dsRNAs) into small interfering RNAs (siRNAs) of 19 to 21 nucleotides (nt) in length, with 2-base 3Ј overhangs (12,16,41,47). The RNA-induced silencing complex (RISC) unwinds duplex siRNAs and selectively incorporates one strand of the pair, known as the guide strand. In the active RISC, the guide strand identifies the target RNA transcript (mRNA) with perfect sequence complementarity. The endonuclease Argonaute2 (Ago2) then cleaves and disrupts the targeted transcript (41). The active RISC includes Dicer, Ago2, TRBP, and PACT. TRBP and PACT are two dsRNAbinding proteins (dsRBPs) that function as partners for Dicer (29), forming a complex with Dicer and Ago2 to achieve siRNA-mediated cleavage of mRNA and facilitate microRNA (miRNA) biogenesis (6,19,20,33). TRBP and PACT also bind the dsRNA-dependent protein k...

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Section: Methodsmentioning

confidence: 99%

Ebolavirus Proteins Suppress the Effects of Small Interfering RNA by Direct Interaction with the Mammalian RNA Interference Pathway

Fabozzi¹,

Nabel²,

Dolan

et al. 2011

J Virol

126

104

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“…It consolidates data from 28 SG centers in USA, Canada, Germany, Isreal, Japan, France and UK, including 9 Protein Structure Initiative centers. PepcDB (Protein Expression Purification and Crystallization DataBase), which was created around 2004, was established as an extension to TargetDB to collect more detailed status information and the experimental details of each step in the protein structure production pipeline [40]. This database stores a complete history of the experimental steps in each production trial besides describing the current target production status.…”

Section: Databasesmentioning

confidence: 99%

Sequence-Based Protein Crystallization Propensity Prediction for Structural Genomics: Review and Comparative Analysis

Kurgan

Mizianty²

2009

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Structural genomics (SG) is an international effort that aims at solving three-dimensional shapes of important biological macro-molecules with primary focus on proteins. One of the main bottlenecks in SG is the ability to produce diffraction quality crystals for X-ray crystallography based protein structure determination. SG pipelines allow for certain flexibility in target selection which motivates development of insilico methods for sequence-based prediction/ assessment of the protein crystallization propensity. We overview existing SG databanks that are used to derive these predictive models and we discuss analytical results concerning protein sequence properties that were discovered to correlate with the ability to form crystals. We also contrast and empirically compare modern sequence-based predictors of crystallization propensity including OB-Score, ParCrys, XtalPred and CRYSTALP2. Our analysis shows that these methods provide useful and complimentary predictions. Although their average accuracy is similar at around 70%, we show that application of a simple majority-vote based ensemble improves accuracy to almost 74%. The best improvements are achieved by combining XtalPred with CRYSTALP2 while OB-Score and ParCrys methods overlap to a larger extend, although they still complement the other two predictors. We also demonstrate that 90% of the protein chains can be correctly predicted by at least one of these methods, which suggests that more accurate ensembles could be built in the future. We believe that current protein crystallization propensity predictors could provide useful input for the target selection procedures utilized by the SG centers.

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“…Information from several metabolic pathway databases and experimentally validated interactions from ChEMBL (Gaulton et al, 2011), PDB (Kouranov et al, 2006) and others sources provides a full picture of the all available data. In order to access the high confidence targets, the interactions with combined score of ≥0.4 were taken into account.…”

Section: Data Collectionmentioning

confidence: 99%

Piper longum: A review of its phytochemicals and their network pharmacological evaluation

Choudhary¹,

Singh²

2017

Preprint

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Absorption Distribution Metabolism Excretion Toxicity ADMETModule and GO analysis AbstractPiper longum L. (P. longum, also called as long pepper) is one of the common culinary herb and has been extensively used as an important constituent of various indigenous medicines, specifically in traditional Indian medicinal system known as Ayurveda. Towards obtaining a global regulatory framework of P. longum's constituents, in this work we first reviewed phytochemicals present in this herb and then studied their pharmacological and medicinal features using network pharmacology approach. We developed high-confidence level tripartite networks consisting of phytochemicals -protein targets -disease association and explain the role of its phytochemicals to various chronic diseases. 7 drug-like phytochemicals in this herb were found as the potential regulators of 5 FDA approved drug targets; and 28 novel drug targets were also reported. 105 phytochemicals were linked with immunomodulatory potency by pathway level mapping in human metabolic network. A sub-network of human PPI regulated by its phytochemicals was derived and various modules in this sub-network were successfully associated with specific diseases.

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The RCSB PDB information portal for structural genomics

Cited by 369 publications

References 15 publications

Ebolavirus Proteins Suppress the Effects of Small Interfering RNA by Direct Interaction with the Mammalian RNA Interference Pathway

Ebolavirus Proteins Suppress the Effects of Small Interfering RNA by Direct Interaction with the Mammalian RNA Interference Pathway

Sequence-Based Protein Crystallization Propensity Prediction for Structural Genomics: Review and Comparative Analysis

Piper longum: A review of its phytochemicals and their network pharmacological evaluation

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