Architecture of a fungal fatty acid synthase at 5 A resolution

Science
Simon JenniN Ban

Abstract

All steps of fatty acid synthesis in fungi are catalyzed by the fatty acid synthase, which forms a 2.6-megadalton alpha6beta6 complex. We have determined the molecular architecture of this multienzyme by fitting the structures of homologous enzymes that catalyze the individual steps of the reaction pathway into a 5 angstrom x-ray crystallographic electron density map. The huge assembly contains two separated reaction chambers, each equipped with three sets of active sites separated by distances up to approximately 130 angstroms, across which acyl carrier protein shuttles substrates during the reaction cycle. Regions of the electron density arising from well-defined structural features outside the catalytic domains separate the two reaction chambers and serve as a matrix in which domains carrying the various active sites are embedded. The structure rationalizes the compartmentalization of fatty acid synthesis, and the spatial arrangement of the active sites has specific implications for our understanding of the reaction cycle mechanism and of the architecture of multienzymes in general.

References

Dec 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·F WielandF Lynen
Jul 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J K StoopsS J Wakil
Jan 1, 1987·Biological Chemistry Hoppe-Seyler·W A Hackenjos, H J Schramm
Jan 1, 1983·Annual Review of Biochemistry·S J WakilV C Joshi
Aug 1, 1980·European Journal of Biochemistry·J L Fox, F Lynen
Aug 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·J K Stoops, S J Wakil
May 15, 1981·European Journal of Biochemistry·K WerkmeisterE Schweizer
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·D W BrownN P Keller
Apr 9, 1998·FEMS Microbiology Letters·C P Woloshuk, R Prieto
Apr 28, 2000·European Journal of Biochemistry·F FichtlschererE Schweizer
Jun 8, 2001·Annual Review of Biochemistry·X HuangF M Raushel
Apr 12, 2003·Progress in Lipid Research·Stuart SmithAnil K Joshi
Sep 9, 2004·Microbiology and Molecular Biology Reviews : MMBR·Eckhart Schweizer, Jörg Hofmann
Sep 17, 2004·The Journal of Biological Chemistry·Matthew S KimberCharles O Rock
Jan 13, 2005·Journal of Molecular Biology·Kristian M KoskiTuomo Glumoff
Jan 18, 2005·Clinical Microbiology Reviews·Kuni TakayamaGurdyal S Besra
Jun 15, 2005·Annual Review of Biochemistry·Stephen W White Rock

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Citations

Nov 10, 2013·Archives of Microbiology·Juthaporn SangwallekSatoshi Harashima
Aug 25, 2010·Quarterly Reviews of Biophysics·Timm MaierNenad Ban
Aug 14, 2010·Journal of the American Chemical Society·Claudio AnselmiJosé D Faraldo-Gómez
May 31, 2013·Journal of the American Chemical Society·Fumihiro IshikawaMichael D Burkart
Jul 27, 2007·Natural Product Reports·Andrew C Mercer, Michael D Burkart
Nov 23, 2007·Natural Product Reports·Neil DixonJason Micklefield
Jun 25, 2009·Chemical Society Reviews·Jordan L Meier, Michael D Burkart
Jul 29, 2009·Natural Product Reports·Alexander Koglin, Christopher T Walsh
Jan 28, 2012·Molecular BioSystems·Swadha Anand, Debasisa Mohanty
Aug 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Patrik JohanssonMartin Grininger
Dec 21, 2007·Acta Crystallographica. Section D, Biological Crystallography·Yong Xiong
Jan 28, 2009·Acta Crystallographica. Section D, Biological Crystallography·Simon Jenni, Nenad Ban
Apr 16, 2008·Biological Reviews of the Cambridge Philosophical Society·Florian Pankewitz, Monika Hilker
May 9, 2007·Antimicrobial Agents and Chemotherapy·Shilpi SharmaAvadhesha Surolia
Dec 7, 2007·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·David M Byers, Huansheng Gong
Oct 31, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jason M CrawfordCraig A Townsend
Dec 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Paul D StraightRoberto Kolter
Apr 19, 2006·Nature Chemical Biology·John E Cronan
Jun 20, 2007·Nature Chemical Biology·Barrie Wilkinson, Jason Micklefield
Aug 30, 2012·Natural Product Reports·John Crosby, Matthew P Crump
Jan 10, 2012·Current Opinion in Biotechnology·Jaclyn M Winter, Yi Tang
Jul 22, 2009·Phytochemistry·Holger Jenke-Kodama, Elke Dittmann
Oct 25, 2008·Current Opinion in Structural Biology·Marc LeibundgutNenad Ban
Aug 12, 2008·Journal of Ethnopharmacology·Fei YuChang-Xiao Liu
Feb 6, 2008·Bioorganic & Medicinal Chemistry Letters·Robert W HaushalterMichael D Burkart
Mar 10, 2016·Acta Crystallographica. Section D, Structural Biology·Bjørn Panyella PedersenPoul Nissen
Oct 19, 2006·Current Opinion in Biotechnology·Jeffrey D Kittendorf, David H Sherman
Apr 23, 2009·The New Phytologist·Marlis ReichAndrea Polle
Jun 14, 2008·Chembiochem : a European Journal of Chemical Biology·Jason M CrawfordCraig A Townsend
Mar 6, 2007·Chembiochem : a European Journal of Chemical Biology·Ye Liu, Steven D Bruner
Mar 22, 2008·Chembiochem : a European Journal of Chemical Biology·Kira J Weissman, Rolf Müller
Aug 11, 2007·Angewandte Chemie·Thomas Kolter
Sep 12, 2006·Protein Science : a Publication of the Protein Society·Patrik JohanssonKristina Bäckbro
Jul 19, 2012·Chembiochem : a European Journal of Chemical Biology·Jennifer Foulke-Abel, Craig A Townsend
Feb 25, 2010·Acta Crystallographica. Section D, Biological Crystallography·Bjørn P PedersenPoul Nissen

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