FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2774700024> ?p ?o ?g. }

• W2774700024 endingPage "288" @default.
• W2774700024 startingPage "273" @default.
• W2774700024 abstract "OXA-239 is a class D carbapenemase isolated from an Acinetobacter baumannii strain found in Mexico. This enzyme is a variant of OXA-23 with three amino acid substitutions in or near the active site. These substitutions cause OXA-239 to hydrolyze late-generation cephalosporins and the monobactam aztreonam with greater efficiency than OXA-23. OXA-239 activity against the carbapenems doripenem and imipenem is reduced ∼3-fold and 20-fold, respectively. Further analysis demonstrated that two of the substitutions (P225S and D222N) are largely responsible for the observed alteration of kinetic parameters, while the third (S109L) may serve to stabilize the protein. Structures of OXA-239 with cefotaxime, doripenem and imipenem bound as acyl-intermediates were determined. These structures reveal that OXA-239 has increased flexibility in a loop that contains P225S and D222N. When carbapenems are bound, the conformation of this loop is essentially identical with that observed previously for OXA-23, with a narrow active site that makes extensive contacts to the ligand. When cefotaxime is bound, the loop can adopt a different conformation that widens the active site to allow binding of that bulky drug. This alternate conformation is made possible by P225S and further stabilized by D222N. Taken together, these results suggest that the three substitutions were selected to expand the substrate specificity profile of OXA-23 to cephalosporins and monobactams. The loss of activity against imipenem, however, suggests that there may be limits to the plasticity of class D enzymes with regard to evolving active sites that can effectively bind multiple classes of β-lactam drugs." @default.
• W2774700024 created "2017-12-22" @default.
• W2774700024 creator A5000611736 @default.
• W2774700024 creator A5007827494 @default.
• W2774700024 creator A5016164351 @default.
• W2774700024 creator A5028655167 @default.
• W2774700024 creator A5032594720 @default.
• W2774700024 creator A5064299843 @default.
• W2774700024 date "2018-01-11" @default.
• W2774700024 modified "2023-09-26" @default.
• W2774700024 title "Multiple substitutions lead to increased loop flexibility and expanded specificity in <i>Acinetobacter baumannii</i> carbapenemase OXA-239" @default.
• W2774700024 cites W1845997799 @default.
• W2774700024 cites W1920890130 @default.
• W2774700024 cites W1964529071 @default.
• W2774700024 cites W1968571268 @default.
• W2774700024 cites W1971186057 @default.
• W2774700024 cites W1972994991 @default.
• W2774700024 cites W1981765089 @default.
• W2774700024 cites W1983164658 @default.
• W2774700024 cites W1987635163 @default.
• W2774700024 cites W1989592886 @default.
• W2774700024 cites W2006246268 @default.
• W2774700024 cites W2011080054 @default.
• W2774700024 cites W2016230165 @default.
• W2774700024 cites W2023751078 @default.
• W2774700024 cites W2025930267 @default.
• W2774700024 cites W2038840577 @default.
• W2774700024 cites W2083021997 @default.
• W2774700024 cites W2083974126 @default.
• W2774700024 cites W2090476725 @default.
• W2774700024 cites W2091069899 @default.
• W2774700024 cites W2097306188 @default.
• W2774700024 cites W2097469356 @default.
• W2774700024 cites W2097719059 @default.
• W2774700024 cites W2099177586 @default.
• W2774700024 cites W2123364796 @default.
• W2774700024 cites W2124026197 @default.
• W2774700024 cites W2124307758 @default.
• W2774700024 cites W2130093647 @default.
• W2774700024 cites W2134442153 @default.
• W2774700024 cites W2143660875 @default.
• W2774700024 cites W2143875572 @default.
• W2774700024 cites W2144081223 @default.
• W2774700024 cites W2149018580 @default.
• W2774700024 cites W2156889390 @default.
• W2774700024 cites W2163341755 @default.
• W2774700024 cites W2171952306 @default.
• W2774700024 cites W2211192799 @default.
• W2774700024 cites W2222312033 @default.
• W2774700024 cites W2327836479 @default.
• W2774700024 cites W2483856419 @default.
• W2774700024 cites W2522867910 @default.
• W2774700024 cites W2599881574 @default.
• W2774700024 cites W4250496609 @default.
• W2774700024 cites W4377077039 @default.
• W2774700024 cites W648076425 @default.
• W2774700024 doi "https://doi.org/10.1042/bcj20170702" @default.
• W2774700024 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5988212" @default.
• W2774700024 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29229762" @default.
• W2774700024 hasPublicationYear "2018" @default.
• W2774700024 type Work @default.
• W2774700024 sameAs 2774700024 @default.
• W2774700024 citedByCount "15" @default.
• W2774700024 countsByYear W27747000242018 @default.
• W2774700024 countsByYear W27747000242019 @default.
• W2774700024 countsByYear W27747000242020 @default.
• W2774700024 countsByYear W27747000242021 @default.
• W2774700024 countsByYear W27747000242022 @default.
• W2774700024 countsByYear W27747000242023 @default.
• W2774700024 crossrefType "journal-article" @default.
• W2774700024 hasAuthorship W2774700024A5000611736 @default.
• W2774700024 hasAuthorship W2774700024A5007827494 @default.
• W2774700024 hasAuthorship W2774700024A5016164351 @default.
• W2774700024 hasAuthorship W2774700024A5028655167 @default.
• W2774700024 hasAuthorship W2774700024A5032594720 @default.
• W2774700024 hasAuthorship W2774700024A5064299843 @default.
• W2774700024 hasBestOaLocation W27747000242 @default.
• W2774700024 hasConcept C181199279 @default.
• W2774700024 hasConcept C185592680 @default.
• W2774700024 hasConcept C2776315533 @default.
• W2774700024 hasConcept C2776685102 @default.
• W2774700024 hasConcept C2777637488 @default.
• W2774700024 hasConcept C2777821550 @default.
• W2774700024 hasConcept C2777870638 @default.
• W2774700024 hasConcept C2778719061 @default.
• W2774700024 hasConcept C2779631663 @default.
• W2774700024 hasConcept C2780416669 @default.
• W2774700024 hasConcept C41183919 @default.
• W2774700024 hasConcept C501593827 @default.
• W2774700024 hasConcept C523546767 @default.
• W2774700024 hasConcept C54355233 @default.
• W2774700024 hasConcept C55493867 @default.
• W2774700024 hasConcept C64778159 @default.
• W2774700024 hasConcept C71240020 @default.
• W2774700024 hasConcept C86803240 @default.
• W2774700024 hasConcept C94665300 @default.
• W2774700024 hasConceptScore W2774700024C181199279 @default.
• W2774700024 hasConceptScore W2774700024C185592680 @default.

• next