FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2056513054> ?p ?o ?g. }

• W2056513054 endingPage "e11195" @default.
• W2056513054 startingPage "e11195" @default.
• W2056513054 abstract "Background Sonic hedgehog (Shh) is a palmitoylated protein that plays key roles in mammalian development and human cancers. Palmitoylation of Shh is required for effective long and short range Shh-mediated signaling. Attachment of palmitate to Shh is catalyzed by Hedgehog acyltransferase (Hhat), a member of the membrane bound O-acyl transferase (MBOAT) family of multipass membrane proteins. The extremely hydrophobic composition of MBOAT proteins has limited their biochemical characterization. Except for mutagenesis of two conserved residues, there has been no structure-function analysis of Hhat, and the regions of the protein required for Shh palmitoylation are unknown. Methodology/Principal Findings Here we undertake a systematic approach to identify residues within Hhat that are required for protein stability and/or enzymatic activity. We also identify a second, novel MBOAT homology region (residues 196–234) that is required for Hhat activity. In total, ten deletion mutants and eleven point mutants were generated and analyzed. Truncations at the N- and C-termini of Hhat yielded inactive proteins with reduced stability. Four Hhat mutants with deletions within predicted loop regions and five point mutants retained stability but lost palmitoylation activity. We purified two point mutants, W378A and H379A, with defective Hhat activity. Kinetic analyses revealed alterations in apparent Km and Vmax for Shh and/or palmitoyl CoA, changes that likely explain the catalytic defects observed for these mutants. Conclusions/Significance This study has pinpointed specific regions and multiple residues that regulate Hhat stability and catalysis. Our findings should be applicable to other MBOAT proteins that mediate lipid modification of Wnt proteins and ghrelin, and should serve as a model for understanding how secreted morphogens are modified by palmitoyl acyltransferases." @default.
• W2056513054 created "2016-06-24" @default.
• W2056513054 creator A5015599531 @default.
• W2056513054 creator A5027044141 @default.
• W2056513054 date "2010-06-23" @default.
• W2056513054 modified "2023-10-16" @default.
• W2056513054 title "Identification of Conserved Regions and Residues within Hedgehog Acyltransferase Critical for Palmitoylation of Sonic Hedgehog" @default.
• W2056513054 cites W1512968077 @default.
• W2056513054 cites W1513667798 @default.
• W2056513054 cites W1541949755 @default.
• W2056513054 cites W1866855833 @default.
• W2056513054 cites W1964837364 @default.
• W2056513054 cites W1971388047 @default.
• W2056513054 cites W1976551834 @default.
• W2056513054 cites W1993396452 @default.
• W2056513054 cites W1994662145 @default.
• W2056513054 cites W1996218285 @default.
• W2056513054 cites W2001553948 @default.
• W2056513054 cites W2002355858 @default.
• W2056513054 cites W2018127398 @default.
• W2056513054 cites W2018886211 @default.
• W2056513054 cites W2026550373 @default.
• W2056513054 cites W2029042594 @default.
• W2056513054 cites W2030943228 @default.
• W2056513054 cites W2045100304 @default.
• W2056513054 cites W2048393066 @default.
• W2056513054 cites W2054251345 @default.
• W2056513054 cites W2057775661 @default.
• W2056513054 cites W2059456940 @default.
• W2056513054 cites W2069528220 @default.
• W2056513054 cites W2078932350 @default.
• W2056513054 cites W2082074319 @default.
• W2056513054 cites W2086751240 @default.
• W2056513054 cites W2095715909 @default.
• W2056513054 cites W2095777272 @default.
• W2056513054 cites W2100505770 @default.
• W2056513054 cites W2111592695 @default.
• W2056513054 cites W2112083470 @default.
• W2056513054 cites W2124711584 @default.
• W2056513054 cites W2126134129 @default.
• W2056513054 cites W2135835127 @default.
• W2056513054 cites W2147864074 @default.
• W2056513054 cites W2150788754 @default.
• W2056513054 cites W2153188090 @default.
• W2056513054 cites W2156416422 @default.
• W2056513054 cites W2162892059 @default.
• W2056513054 cites W2163221665 @default.
• W2056513054 cites W2167670101 @default.
• W2056513054 cites W2186677746 @default.
• W2056513054 cites W2336529048 @default.
• W2056513054 doi "https://doi.org/10.1371/journal.pone.0011195" @default.
• W2056513054 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2890405" @default.
• W2056513054 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20585641" @default.
• W2056513054 hasPublicationYear "2010" @default.
• W2056513054 type Work @default.
• W2056513054 sameAs 2056513054 @default.
• W2056513054 citedByCount "51" @default.
• W2056513054 countsByYear W20565130542012 @default.
• W2056513054 countsByYear W20565130542013 @default.
• W2056513054 countsByYear W20565130542014 @default.
• W2056513054 countsByYear W20565130542015 @default.
• W2056513054 countsByYear W20565130542016 @default.
• W2056513054 countsByYear W20565130542017 @default.
• W2056513054 countsByYear W20565130542018 @default.
• W2056513054 countsByYear W20565130542019 @default.
• W2056513054 countsByYear W20565130542020 @default.
• W2056513054 countsByYear W20565130542021 @default.
• W2056513054 countsByYear W20565130542022 @default.
• W2056513054 countsByYear W20565130542023 @default.
• W2056513054 crossrefType "journal-article" @default.
• W2056513054 hasAuthorship W2056513054A5015599531 @default.
• W2056513054 hasAuthorship W2056513054A5027044141 @default.
• W2056513054 hasBestOaLocation W20565130541 @default.
• W2056513054 hasConcept C104317684 @default.
• W2056513054 hasConcept C143065580 @default.
• W2056513054 hasConcept C145837895 @default.
• W2056513054 hasConcept C146727910 @default.
• W2056513054 hasConcept C176944494 @default.
• W2056513054 hasConcept C181199279 @default.
• W2056513054 hasConcept C2775970874 @default.
• W2056513054 hasConcept C2776637008 @default.
• W2056513054 hasConcept C2778539099 @default.
• W2056513054 hasConcept C2779201268 @default.
• W2056513054 hasConcept C55493867 @default.
• W2056513054 hasConcept C62478195 @default.
• W2056513054 hasConcept C86803240 @default.
• W2056513054 hasConcept C88498014 @default.
• W2056513054 hasConcept C95444343 @default.
• W2056513054 hasConceptScore W2056513054C104317684 @default.
• W2056513054 hasConceptScore W2056513054C143065580 @default.
• W2056513054 hasConceptScore W2056513054C145837895 @default.
• W2056513054 hasConceptScore W2056513054C146727910 @default.
• W2056513054 hasConceptScore W2056513054C176944494 @default.
• W2056513054 hasConceptScore W2056513054C181199279 @default.
• W2056513054 hasConceptScore W2056513054C2775970874 @default.
• W2056513054 hasConceptScore W2056513054C2776637008 @default.
• W2056513054 hasConceptScore W2056513054C2778539099 @default.
• W2056513054 hasConceptScore W2056513054C2779201268 @default.

• next