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A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family
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2017 (Engelska)Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, nr 1, artikel-id 1541Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes. To a certain extent, their substrate preference redundancies correlate with structural classes, thus linking structure and activity relationships. To elucidate interdependence among the NUDIX hydrolases, we pairwise deplete them generating an epistatic interaction map, evaluate cell cycle perturbations upon knockdown in normal and cancer cells, and analyse their protein and mRNA expression in normal and cancer tissues. Using a novel FUSION algorithm, we integrate all data creating a comprehensive NUDIX enzyme profile map, which will prove fundamental to understanding their biological functionality.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group , 2017. Vol. 8, nr 1, artikel-id 1541
Nyckelord [en]
Nudix hydrolase, NUDT1 protein, NUDT10 protein, NUDT11 protein, NUDT12 protein, NUDT13 protein, NUDT14 protein, NUDT16 protein, NUDT17 protein, NUDT19 protein, NUDT20 protein, NUDT21 protein, NUDT22 protein, NUDT4 protein, NUDT5 protein, NUDT6 protein, NUDT7 protein, NUDT8 protein, unclassified drug, algorithm, biochemical composition, cancer, enzyme, enzyme activity, gene expression, homeostasis, metabolism, protein, A-549 cell line, Article, breast cancer, cancer cell line, cancer tissue, cell cycle, cell cycle regulation, cell survival, colorectal cancer, controlled study, DNA content, enzyme structure, functional genomics, gene interaction, gene silencing, human, human cell, human tissue, immunohistochemistry, melanoma, phylogenetic tree, protein expression, sequence alignment, tissue microarray, upregulation
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
URN: urn:nbn:se:kth:diva-227131DOI: 10.1038/s41467-017-01642-wISI: 000415323000014PubMedID: 29142246Scopus ID: 2-s2.0-85034433549OAI: oai:DiVA.org:kth-227131DiVA, id: diva2:1203536
Anmärkning

QC 20180503

Tillgänglig från: 2018-05-03 Skapad: 2018-05-03 Senast uppdaterad: 2019-09-20Bibliografiskt granskad

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Hallström, Björn M.Lundberg, Emma

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Hallström, Björn M.Ait Blal, HammouLundberg, Emma
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Science for Life Laboratory, SciLifeLab
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Nature Communications
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

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