FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1998452839> ?p ?o ?g. }

• W1998452839 endingPage "2134" @default.
• W1998452839 startingPage "2123" @default.
• W1998452839 abstract "To understand the molecular basis of sequential N-dealkylation by cytochrome P450 2B enzymes, we studied the binding of amidopyrine (AP) as well as the metabolites of this reaction, desmethylamidopyrine (DMAP) and aminoantipyrine (AAP), using the X-ray crystal structure of rabbit P450 2B4 and two nuclear magnetic resonance (NMR) techniques: saturation transfer difference (STD) spectroscopy and longitudinal (T1) relaxation NMR. Results of STD NMR of AP and its metabolites bound to P450 2B4 were similar, suggesting that they occupy similar niches within the enzyme’s active site. The model-dependent relaxation rates (RM) determined from T1 relaxation NMR of AP and DMAP suggest that the N-linked methyl is closest to the heme. To determine the orientation(s) of AP and its metabolites within the P450 2B4 active site, we used distances calculated from the relaxation rates to constrain the metabolites to the X-ray crystal structure of P450 2B4. Simulated annealing of the complex revealed that the metabolites do indeed occupy similar hydrophobic pockets within the active site, while the N-linked methyls are free to rotate between two binding modes. From these bound structures, a model of N-demethylation in which the N-linked methyl functional groups rotate between catalytic and noncatalytic positions was developed. This study is the first to provide a structural model of a drug and its metabolites complexed to a cytochrome P450 based on NMR and to provide a structural mechanism for how a drug can undergo sequential oxidations without unbinding. The rotation of the amide functional group might represent a common structural mechanism for N-dealkylation reactions for other drugs such as the local anesthetic lidocaine." @default.
• W1998452839 created "2016-06-24" @default.
• W1998452839 creator A5017283393 @default.
• W1998452839 creator A5033645297 @default.
• W1998452839 creator A5044026012 @default.
• W1998452839 creator A5050736930 @default.
• W1998452839 creator A5054591348 @default.
• W1998452839 creator A5058650202 @default.
• W1998452839 date "2011-03-04" @default.
• W1998452839 modified "2023-09-27" @default.
• W1998452839 title "NMR-Derived Models of Amidopyrine and Its Metabolites in Complexes with Rabbit Cytochrome P450 2B4 Reveal a Structural Mechanism of Sequential N-Dealkylation" @default.
• W1998452839 cites W1532212858 @default.
• W1998452839 cites W1541210234 @default.
• W1998452839 cites W1541515816 @default.
• W1998452839 cites W1595414536 @default.
• W1998452839 cites W1890201160 @default.
• W1998452839 cites W1965428124 @default.
• W1998452839 cites W1970519842 @default.
• W1998452839 cites W1972453313 @default.
• W1998452839 cites W1972459558 @default.
• W1998452839 cites W1974543768 @default.
• W1998452839 cites W1975786509 @default.
• W1998452839 cites W1976312818 @default.
• W1998452839 cites W1979131204 @default.
• W1998452839 cites W1982736602 @default.
• W1998452839 cites W1986191731 @default.
• W1998452839 cites W1988393381 @default.
• W1998452839 cites W1991708137 @default.
• W1998452839 cites W1993418191 @default.
• W1998452839 cites W1993837640 @default.
• W1998452839 cites W1994830533 @default.
• W1998452839 cites W1997224684 @default.
• W1998452839 cites W1998177378 @default.
• W1998452839 cites W1998342457 @default.
• W1998452839 cites W2000524760 @default.
• W1998452839 cites W2002638212 @default.
• W1998452839 cites W2004363592 @default.
• W1998452839 cites W2005470532 @default.
• W1998452839 cites W2006422372 @default.
• W1998452839 cites W2009881858 @default.
• W1998452839 cites W2010617676 @default.
• W1998452839 cites W2011293379 @default.
• W1998452839 cites W2014051487 @default.
• W1998452839 cites W2014860988 @default.
• W1998452839 cites W2015219850 @default.
• W1998452839 cites W2019960920 @default.
• W1998452839 cites W2022246634 @default.
• W1998452839 cites W2024574068 @default.
• W1998452839 cites W2038526015 @default.
• W1998452839 cites W2043662478 @default.
• W1998452839 cites W2046976976 @default.
• W1998452839 cites W2051412494 @default.
• W1998452839 cites W2054256187 @default.
• W1998452839 cites W2060907949 @default.
• W1998452839 cites W2061151008 @default.
• W1998452839 cites W2064602409 @default.
• W1998452839 cites W2064911880 @default.
• W1998452839 cites W2065209479 @default.
• W1998452839 cites W2067174909 @default.
• W1998452839 cites W2074054277 @default.
• W1998452839 cites W2074467632 @default.
• W1998452839 cites W2077451485 @default.
• W1998452839 cites W2090991101 @default.
• W1998452839 cites W2092511209 @default.
• W1998452839 cites W2093934432 @default.
• W1998452839 cites W2094080800 @default.
• W1998452839 cites W2094204330 @default.
• W1998452839 cites W2100073637 @default.
• W1998452839 cites W2100748232 @default.
• W1998452839 cites W2104180764 @default.
• W1998452839 cites W2108683812 @default.
• W1998452839 cites W2122368088 @default.
• W1998452839 cites W2127151102 @default.
• W1998452839 cites W2130434638 @default.
• W1998452839 cites W2159307624 @default.
• W1998452839 cites W2168076340 @default.
• W1998452839 cites W2168235332 @default.
• W1998452839 cites W2171268876 @default.
• W1998452839 cites W2413742506 @default.
• W1998452839 cites W277290643 @default.
• W1998452839 cites W315960372 @default.
• W1998452839 cites W95014119 @default.
• W1998452839 cites W994970986 @default.
• W1998452839 doi "https://doi.org/10.1021/bi101797v" @default.
• W1998452839 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3163098" @default.
• W1998452839 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21375273" @default.
• W1998452839 hasPublicationYear "2011" @default.
• W1998452839 type Work @default.
• W1998452839 sameAs 1998452839 @default.
• W1998452839 citedByCount "11" @default.
• W1998452839 countsByYear W19984528392012 @default.
• W1998452839 countsByYear W19984528392013 @default.
• W1998452839 countsByYear W19984528392014 @default.
• W1998452839 countsByYear W19984528392015 @default.
• W1998452839 countsByYear W19984528392016 @default.
• W1998452839 countsByYear W19984528392018 @default.
• W1998452839 countsByYear W19984528392020 @default.
• W1998452839 crossrefType "journal-article" @default.

• next