The Pfam protein families database in 2019

El-Gebali, Sara; Mistry, Jaina; Bateman, Alex; Eddy, Sean R.; Luciani, Aurélien; Potter, Simon; Qureshi, Matloob; Richardson, Lorna; Salazar, Gustavo; Smart, Alfredo; Sonnhammer, Erik L. L.; Hirsh, Layla; Paladin, Lisanna; Piovesan, Damiano; Tosatto, Silvio C. E.

doi:10.1093/nar/gky995

Cited by 4,169 publications

(3,644 citation statements)

References 23 publications

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“…In contrast, the multimeric state of the middle part of the protein (D2‐D3) was unclear. The second domain had no reliable multimeric templates and was even annotated as a monomer in PFAM (PFAM: PF00275) . The information on the third domain was sparse.…”

Section: Resultsmentioning

confidence: 99%

Structural modeling of protein complexes: Current capabilities and challenges

2019

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Proteins frequently interact with each other, and the knowledge of structures of the corresponding protein complexes is necessary to understand how they function. Computational methods are increasingly used to provide structural models of protein complexes. Not surprisingly, community‐wide Critical Assessment of protein Structure Prediction (CASP) experiments have recently started monitoring the progress in this research area. We participated in CASP13 with the aim to evaluate our current capabilities in modeling of protein complexes and to gain a better understanding of factors that exert the largest impact on these capabilities. To model protein complexes in CASP13, we applied template‐based modeling, free docking and hybrid techniques that enabled us to generate models of the topmost quality for 27 of 42 multimers. If templates for protein complexes could be identified, we modeled the structures with reasonable accuracy by straightforward homology modeling. If only partial templates were available, it was nevertheless possible to predict the interaction interfaces correctly or to generate acceptable models for protein complexes by combining template‐based modeling with docking. If no templates were available, we used rigid‐body docking with limited success. However, in some free docking models, despite the incorrect subunit orientation and missed interface contacts, the approximate location of protein binding sites was identified correctly. Apparently, our overall performance in docking was limited by the quality of monomer models and by the imperfection of scoring methods. The impact of human intervention on our results in modeling of protein complexes was significant indicating the need for improvements of automatic methods.

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Section: Resultsmentioning

confidence: 99%

Structural modeling of protein complexes: Current capabilities and challenges

2019

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“…Wheat coding sequence (CDS) predictions, refmap comparison between IWGSC and The Genome Analysis Centre (TGAC) and functional annotations of both high and low confidence (HC and LC) wheat genes were downloaded from the IWGSC archive v.1.0 (https://urgi.versailles.inra.fr/download/iwgsc/IWGSC_RefSeq_Annotations/v1.0/) (IWGSC, ) and the CSS–TGAC comparison was downloaded from https://opendata.earlham.ac.uk/opendata/data/Triticum_aestivum/TGAC/v1/annotation/ (Clavijo et al ., ). Functional annotations were filtered for Protein family database (Pfam) identifiers of the MADS and K domains (PF00319 and PF01486), respectively (El‐Gebali et al ., ). A total of 439 sequences were identified (see a list of all gene IDs in Supporting Information Table S1).…”

Section: Methodsmentioning

confidence: 97%

Genome‐wide analysis of MIKC‐type MADS‐box genes in wheat: pervasive duplications, functional conservation and putative neofunctionalization

et al. 2019

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Summary Wheat (Triticum aestivum) is one of the most important crops worldwide. Given a growing global population coupled with increasingly challenging cultivation conditions, facilitating wheat breeding by fine‐tuning important traits is of great importance. MADS‐box genes are prime candidates for this, as they are involved in virtually all aspects of plant development. Here, we present a detailed overview of phylogeny and expression of 201 wheat MIKC‐type MADS‐box genes. Homoeolog retention is significantly above the average genome‐wide retention rate for wheat genes, indicating that many MIKC‐type homoeologs are functionally important and not redundant. Gene expression is generally in agreement with the expected subfamily‐specific expression pattern, indicating broad conservation of function of MIKC‐type genes during wheat evolution. We also found extensive expansion of some MIKC‐type subfamilies, especially those potentially involved in adaptation to different environmental conditions like flowering time genes. Duplications are especially prominent in distal telomeric regions. A number of MIKC‐type genes show novel expression patterns and respond, for example, to biotic stress, pointing towards neofunctionalization. We speculate that conserved, duplicated and neofunctionalized MIKC‐type genes may have played an important role in the adaptation of wheat to a diversity of conditions, hence contributing to the importance of wheat as a global staple food.

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“…ANT(4′)‐IIb shared relatively low sequence identity with other ANTs despite the presence of a conserved NT sequence motif (Pfam). To investigate how this primary sequence variation is reflected in the protein structure, we compared the ANT(4′)‐IIb crystal structures to available structural homologues.…”

Section: Resultsmentioning

confidence: 99%

Structural characterization of aminoglycoside 4′‐O‐adenylyltransferase ANT(4′)‐IIb from Pseudomonas aeruginosa

et al. 2020

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Aminoglycosides were one of the first classes of broad‐spectrum antibacterial drugs clinically used to effectively combat infections. The rise of resistance to these drugs, mediated by enzymatic modification, has since compromised their utility as a treatment option, prompting intensive research into the molecular function of resistance enzymes. Here, we report the crystal structure of aminoglycoside nucleotidyltransferase ANT(4′)‐IIb in apo and tobramycin‐bound forms at a resolution of 1.6 and 2.15 Å, respectively. ANT(4′)‐IIb was discovered in the opportunistic pathogen Pseudomonas aeruginosa and conferred resistance to amikacin and tobramycin. Analysis of the ANT(4′)‐IIb structures revealed a two‐domain organization featuring a mixed β‐sheet and an α‐helical bundle. ANT(4′)‐IIb monomers form a dimer required for its enzymatic activity, as coordination of the aminoglycoside substrate relies on residues contributed by both monomers. Despite harbouring appreciable primary sequence diversity compared to previously characterized homologues, the ANT(4′)‐IIb structure demonstrates a surprising level of structural conservation highlighting the high plasticity of this general protein fold. Site‐directed mutagenesis of active site residues and kinetic analysis provides support for a catalytic mechanism similar to those of other nucleotidyltransferases. Using the molecular insights provided into this ANT(4′)‐IIb‐represented enzymatic group, we provide a hypothesis for the potential evolutionary origin of these aminoglycoside resistance determinants.

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The Pfam protein families database in 2019

Cited by 4,169 publications

References 23 publications

Structural modeling of protein complexes: Current capabilities and challenges

Structural modeling of protein complexes: Current capabilities and challenges

Genome‐wide analysis of MIKC‐type MADS‐box genes in wheat: pervasive duplications, functional conservation and putative neofunctionalization

Structural characterization of aminoglycoside 4′‐O‐adenylyltransferase ANT(4′)‐IIb from Pseudomonas aeruginosa

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