PhyreStorm: A Web Server for Fast Structural Searches Against the PDB

Mezulis, Stefans; Sternberg, Michael J.E.; Kelley, Lawrence A.

doi:10.1016/j.jmb.2015.10.017

Cited by 15 publications

(9 citation statements)

References 24 publications

(32 reference statements)

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“…A partial structural model for mouse TRPM7 was developed using homology modeling methods implemented by Phyre2 ( 74 , 75 ). The α kinase domain, as well as regions of TRPM7 primary structure for which satisfactory structural homologs could not be identified, are not included in our model.…”

Section: Methodsmentioning

confidence: 99%

Depletion of plasma membrane–associated phosphoinositides mimics inhibition of TRPM7 channels by cytosolic Mg2+, spermine, and pH

Zhelay¹,

Wieczerzak²,

Beesetty³

et al. 2018

Journal of Biological Chemistry

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Transient receptor potential cation channel subfamily M member 7 (TRPM7) is an ion channel/protein kinase belonging to the TRP melastatin and eEF2 kinase families. Under physiological conditions, most native TRPM7 channels are inhibited by cytoplasmic Mg2+, protons, and polyamines. Currents through these channels (ITRPM7) are robustly potentiated when the cell interior is exchanged with low Mg2+-containing buffers. ITRPM7 is also potentiated by phosphatidyl inositol bisphosphate (PI(4,5)P2) and suppressed by its hydrolysis. Here we characterized internal Mg2+- and pH-mediated inhibition of TRPM7 channels in HEK293 cells overexpressing WT voltage-sensing phospholipid phosphatase (VSP) or its catalytically inactive variant VSP-C363S. VSP-mediated depletion of membrane phosphoinositides significantly increased channel sensitivity to Mg2+ and pH. Proton concentrations that were too low to inhibit ITRPM7 when the VSP-C363S variant was expressed (pH 8.2) became inhibitory in WT VSP–expressing cells. At pH 6.5, protons inhibited ITRPM7 both in WT and VSP C363S–expressing cells but with a faster time course in the WT VSP–expressing cells. Inhibition by 150 μm Mg2+ was also significantly faster in the WT VSP–expressing cells. Cellular PI(4,5)P2 depletion increased the sensitivity of TRPM7 channels to the inhibitor 2-aminoethyl diphenyl borinate, which acidifies the cytosol. Single substitutions at Ser-1107 of TRPM7, reducing its sensitivity to Mg2+, also decreased its inhibition by spermine and acidic pH. Furthermore, these channel variants were markedly less sensitive to VSP-mediated PI(4,5)P2 depletion than the WT. We conclude that the internal Mg2+-, polyamine-, and pH-mediated inhibition of TRPM7 channels is not direct but, rather, reflects electrostatic screening and resultant disruption of PI(4,5)P2–channel interactions.

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Section: Methodsmentioning

confidence: 99%

Depletion of plasma membrane–associated phosphoinositides mimics inhibition of TRPM7 channels by cytosolic Mg2+, spermine, and pH

Zhelay¹,

Wieczerzak²,

Beesetty³

et al. 2018

Journal of Biological Chemistry

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“…The secondary structural features are illustrated in a structural homology model of As37 using ESPript [26]. The secondary structure elements were generated by homology modeling with either Phyre2 [27,28] or Swiss model [29]. Phylogenetic trees were generated for those functional protein homologs identified in this study using Phylogeny.fr [30].…”

Section: Sequence Alignment and Analysismentioning

confidence: 99%

Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection

et al. 2020

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Background Ascaris lumbricoides is one of the three major soil-transmitted gastrointestinal helminths (STHs) that infect more than 440 million people in the world, ranking this neglected tropical disease among the most common afflictions of people living in poverty. Children infected with this roundworm suffer from malnutrition, growth stunting as well as cognitive and intellectual deficits. An effective vaccine is urgently needed to complement anthelmintic deworming as a better approach to control helminth infections. As37 is an immunodominant antigen of Ascaris suum, a pig roundworm closely related to the human A. lumbricoides parasite, recognized by protective immune sera from A. suum infected mice. In this study, the immunogenicity and vaccine efficacy of recombinant As37 were evaluated in a mouse model.

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“…The most accurate method is to run one-against-all pairwise structure alignment, which is too slow to be practical. Some methods were developed to keep a balance between the speed and the accuracy, including Dali server ( 2 , 12 , 13 ), SSM ( 14 ), PhyreStorm ( 15 ) and FATCAT ( 16 ). Most search tools are for rigid monomer structures while there is a method TopSearch for complex structure search ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

mTM-align: a server for fast protein structure database search and multiple protein structure alignment

Dong

Pan

Peng

et al. 2018

Nucleic Acids Research

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With the rapid increase of the number of protein structures in the Protein Data Bank, it becomes urgent to develop algorithms for efficient protein structure comparisons. In this article, we present the mTM-align server, which consists of two closely related modules: one for structure database search and the other for multiple structure alignment. The database search is speeded up based on a heuristic algorithm and a hierarchical organization of the structures in the database. The multiple structure alignment is performed using the recently developed algorithm mTM-align. Benchmark tests demonstrate that our algorithms outperform other peering methods for both modules, in terms of speed and accuracy. One of the unique features for the server is the interplay between database search and multiple structure alignment. The server provides service not only for performing fast database search, but also for making accurate multiple structure alignment with the structures found by the search. For the database search, it takes about 2–5 min for a structure of a medium size (∼300 residues). For the multiple structure alignment, it takes a few seconds for ∼10 structures of medium sizes. The server is freely available at: http://yanglab.nankai.edu.cn/mTM-align/.

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PhyreStorm: A Web Server for Fast Structural Searches Against the PDB

Cited by 15 publications

References 24 publications

Depletion of plasma membrane–associated phosphoinositides mimics inhibition of TRPM7 channels by cytosolic Mg2+, spermine, and pH

Depletion of plasma membrane–associated phosphoinositides mimics inhibition of TRPM7 channels by cytosolic Mg2+, spermine, and pH

Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection

mTM-align: a server for fast protein structure database search and multiple protein structure alignment

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