FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2094201906> ?p ?o ?g. }

• W2094201906 endingPage "2696" @default.
• W2094201906 startingPage "2687" @default.
• W2094201906 abstract "The aconitase family of hydro-lyase enzymes includes three classes of proteins that catalyze the isomerization of alpha-hydroxy acids to beta-hydroxy acids. Besides aconitase, isopropylmalate isomerase (IPMI) proteins specifically catalyze the isomerization of alpha,beta-dicarboxylates with hydrophobic gamma-chain groups, and homoaconitase (HACN) proteins catalyze the isomerization of tricarboxylates with variable chain length gamma-carboxylate groups. These enzymes' stereospecific hydro-lyase activities make them attractive catalysts to produce diastereomers from unsaturated precursors. However, sequence similarity and convergent evolution among these proteins lead to widespread misannotation and uncertainty about gene function. To find the substrate specificity determinants of homologous IPMI and HACN proteins from Methanocaldococcus jannaschii, the small-subunit HACN protein (MJ1271) was crystallized for X-ray diffraction. The structural model showed characteristic residues in a flexible loop region between alpha2 and alpha3 that distinguish HACN from IPMI and aconitase proteins. Site-directed mutagenesis of MJ1271 produced loop-region variant proteins that were reconstituted with wild-type MJ1003 large-subunit protein. The heteromers formed promiscuous hydro-lyases with reduced activity but broader substrate specificity. Both R26K and R26V variants formed relatively efficient IPMI enzymes, while the T27A variant had uniformly lower specificity constants for both IPMI and HACN substrates. The R26V T27Y variant resembles the MJ1277 IPMI small subunit in its flexible loop sequence but demonstrated the broad substrate specificity of the R26V variant. These mutations may reverse the evolution of HACN activity from an ancestral IPMI gene, demonstrating the evolutionary potential for promiscuity in hydro-lyase enzymes. Understanding these specificity determinants enables the functional reannotation of paralogous HACN and IPMI genes in numerous genome sequences. These structural and kinetic results will help to engineer new stereospecific hydro-lyase enzymes for chemoenzymatic syntheses." @default.
• W2094201906 created "2016-06-24" @default.
• W2094201906 creator A5001035619 @default.
• W2094201906 creator A5025116997 @default.
• W2094201906 creator A5027781657 @default.
• W2094201906 creator A5040532393 @default.
• W2094201906 creator A5042294090 @default.
• W2094201906 creator A5047992449 @default.
• W2094201906 creator A5075565913 @default.
• W2094201906 creator A5082004741 @default.
• W2094201906 date "2010-03-03" @default.
• W2094201906 modified "2023-09-30" @default.
• W2094201906 title "Substrate Specificity Determinants of the Methanogen Homoaconitase Enzyme: Structure and Function of the Small Subunit^," @default.
• W2094201906 cites W1539796472 @default.
• W2094201906 cites W1596833660 @default.
• W2094201906 cites W1649558887 @default.
• W2094201906 cites W1969383250 @default.
• W2094201906 cites W1971794083 @default.
• W2094201906 cites W1976261957 @default.
• W2094201906 cites W1980153303 @default.
• W2094201906 cites W1986191025 @default.
• W2094201906 cites W1986274241 @default.
• W2094201906 cites W1987816347 @default.
• W2094201906 cites W1992625839 @default.
• W2094201906 cites W1995017064 @default.
• W2094201906 cites W1998238795 @default.
• W2094201906 cites W2003161010 @default.
• W2094201906 cites W2008921808 @default.
• W2094201906 cites W2014694459 @default.
• W2094201906 cites W2018035730 @default.
• W2094201906 cites W2020436787 @default.
• W2094201906 cites W2030645245 @default.
• W2094201906 cites W2045924603 @default.
• W2094201906 cites W2048351435 @default.
• W2094201906 cites W2054271955 @default.
• W2094201906 cites W2058191052 @default.
• W2094201906 cites W2060809301 @default.
• W2094201906 cites W2080476827 @default.
• W2094201906 cites W2082154678 @default.
• W2094201906 cites W2083586843 @default.
• W2094201906 cites W2089119194 @default.
• W2094201906 cites W2107604376 @default.
• W2094201906 cites W2117514600 @default.
• W2094201906 cites W2133476699 @default.
• W2094201906 cites W2135900956 @default.
• W2094201906 cites W2139891610 @default.
• W2094201906 cites W2142299594 @default.
• W2094201906 cites W2144081223 @default.
• W2094201906 cites W2144362290 @default.
• W2094201906 cites W2152349129 @default.
• W2094201906 cites W2158266834 @default.
• W2094201906 cites W2160355621 @default.
• W2094201906 cites W2163089766 @default.
• W2094201906 cites W2165173856 @default.
• W2094201906 cites W2337435969 @default.
• W2094201906 cites W2403440933 @default.
• W2094201906 cites W4238613043 @default.
• W2094201906 doi "https://doi.org/10.1021/bi901766z" @default.
• W2094201906 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20170198" @default.
• W2094201906 hasPublicationYear "2010" @default.
• W2094201906 type Work @default.
• W2094201906 sameAs 2094201906 @default.
• W2094201906 citedByCount "10" @default.
• W2094201906 countsByYear W20942019062012 @default.
• W2094201906 countsByYear W20942019062013 @default.
• W2094201906 countsByYear W20942019062014 @default.
• W2094201906 countsByYear W20942019062016 @default.
• W2094201906 countsByYear W20942019062020 @default.
• W2094201906 countsByYear W20942019062021 @default.
• W2094201906 countsByYear W20942019062023 @default.
• W2094201906 crossrefType "journal-article" @default.
• W2094201906 hasAuthorship W2094201906A5001035619 @default.
• W2094201906 hasAuthorship W2094201906A5025116997 @default.
• W2094201906 hasAuthorship W2094201906A5027781657 @default.
• W2094201906 hasAuthorship W2094201906A5040532393 @default.
• W2094201906 hasAuthorship W2094201906A5042294090 @default.
• W2094201906 hasAuthorship W2094201906A5047992449 @default.
• W2094201906 hasAuthorship W2094201906A5075565913 @default.
• W2094201906 hasAuthorship W2094201906A5082004741 @default.
• W2094201906 hasConcept C104292427 @default.
• W2094201906 hasConcept C104317684 @default.
• W2094201906 hasConcept C143065580 @default.
• W2094201906 hasConcept C16318435 @default.
• W2094201906 hasConcept C167625842 @default.
• W2094201906 hasConcept C181199279 @default.
• W2094201906 hasConcept C185592680 @default.
• W2094201906 hasConcept C200886947 @default.
• W2094201906 hasConcept C2777269803 @default.
• W2094201906 hasConcept C2781264208 @default.
• W2094201906 hasConcept C2781374117 @default.
• W2094201906 hasConcept C41183919 @default.
• W2094201906 hasConcept C55493867 @default.
• W2094201906 hasConcept C71240020 @default.
• W2094201906 hasConcept C86803240 @default.
• W2094201906 hasConceptScore W2094201906C104292427 @default.
• W2094201906 hasConceptScore W2094201906C104317684 @default.
• W2094201906 hasConceptScore W2094201906C143065580 @default.
• W2094201906 hasConceptScore W2094201906C16318435 @default.

• next