A mechanism of drug action revealed by structural studies of enoyl reductase

Science
C BaldockD W Rice

Abstract

Enoyl reductase (ENR), an enzyme involved in fatty acid biosynthesis, is the target for antibacterial diazaborines and the front-line antituberculosis drug isoniazid. Analysis of the structures of complexes of Escherichia coli ENR with nicotinamide adenine dinucleotide and either thienodiazaborine or benzodiazaborine revealed the formation of a covalent bond between the 2' hydroxyl of the nicotinamide ribose and a boron atom in the drugs to generate a tight, noncovalently bound bisubstrate analog. This analysis has implications for the structure-based design of inhibitors of ENR, and similarities to other oxidoreductases suggest that mimicking this molecular linkage may have generic applications in other areas of medicinal chemistry.

References

Oct 1, 1992·Journal of General Microbiology·H BerglerF Turnowsky
Jan 1, 1985·Methods in Enzymology·R Hamlin
Aug 1, 1984·Journal of Medicinal Chemistry·M A GrassbergerJ Hildebrandt
Oct 22, 1981·Nature·G Högenauer, M Woisetschläger
Feb 1, 1995·Protein Engineering·A C WallaceJ M Thornton
Oct 1, 1994·Trends in Microbiology·S T Cole
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4

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Citations

Jan 20, 2009·Cellular and Molecular Life Sciences : CMLS·R P Massengo-Tiassé, J E Cronan
Nov 13, 2003·European Journal of Pharmacology·George R Uhl, Zhicheng Lin
Nov 9, 2000·FEBS Letters·T FawcettA R Slabas
Oct 10, 2001·Progress in Lipid Research·R J HeathC O Rock
Apr 12, 2003·Progress in Lipid Research·Stuart SmithAnil K Joshi
Jan 1, 1999·Bioorganic & Medicinal Chemistry Letters·M C DavisA R Martin
Jan 16, 2008·Accounts of Chemical Research·Hao Lu, Peter J Tonge
Jun 29, 2012·Journal of the American Chemical Society·Khalid AlKaabiRoald Hoffmann
Aug 12, 2010·Journal of Medicinal Chemistry·Suresh K TipparajuRima L McLeod
Jul 4, 1998·Natural Product Reports·B J Rawlings
Aug 29, 2013·Lab on a Chip·Andreas MenzelMargit Zacharias
Nov 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Xingye YuChaitan Khosla
Jan 17, 2003·Journal of Biomolecular Structure & Dynamics·Jayaraman MuralidharanNamita Surolia
Mar 12, 2011·The Journal of Antimicrobial Chemotherapy·Nina LiuPeter J Tonge
Sep 11, 2001·American Journal of Therapeutics·M P Groziak
Mar 1, 2007·Acta Crystallographica. Section D, Biological Crystallography·Stephen P MuenchDavid W Rice
Mar 3, 2007·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Kook-Han KimEunice EunKyeong Kim
Nov 4, 2010·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Shahila MehboobMichael E Johnson
Mar 24, 2012·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Tae-O KimYong-Seok Heo
Oct 3, 2012·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·José M OteroMark J van Raaij
Dec 14, 1999·Protein Science : a Publication of the Protein Society·X QiuS S Abdel-Meguid
Sep 19, 2007·Antimicrobial Agents and Chemotherapy·Tatiana BogdanovichPeter C Appelbaum
Sep 6, 2012·Antimicrobial Agents and Chemotherapy·Nachum KaplanHenry W Pauls
Sep 18, 2002·Antimicrobial Agents and Chemotherapy·David J PayneWilliam F Huffman
Jun 15, 2005·Annual Review of Biochemistry·Stephen W White Rock
Jul 28, 2012·International Journal of Molecular Sciences·Xiaoyun LuQidong You
Oct 1, 2009·Future Medicinal Chemistry·Stephen J BakerYi Xia
Sep 19, 2012·EMBO Molecular Medicine·Ruben C HartkoornStewart T Cole
Dec 2, 2015·The Journal of Organic Chemistry·Milovan Stojanović, Marija Baranac-Stojanović
Aug 31, 2010·Biochemical and Biophysical Research Communications·Su Jin KimEunice Eunkyeong Kim
Aug 19, 2014·The Journal of Organic Chemistry·Gary A Molander, Steven R Wisniewski
Dec 20, 2008·Protein Expression and Purification·Lisa WenAshish K Pathak
May 7, 2008·Bioorganic & Medicinal Chemistry Letters·Christopher W am EndePeter J Tonge
Dec 4, 2015·Acta Crystallographica. Section C, Structural Chemistry·Evan A SarinaMichael P Groziak

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