Crystal structure of dimeric FabZ of Plasmodium falciparum reveals conformational switching to active hexamers by peptide flips

FEBS Letters
P Lakshmi SwarnamukhiKaza Suguna

Abstract

The crystal structure of beta-hydroxyacyl acyl carrier protein dehydratase of Plasmodium falciparum (PfFabZ) has been determined at a resolution of 2.4 A. PfFabZ has been found to exist as a homodimer (d-PfFabZ) in the crystals of the present study in contrast to the reported hexameric form (h-PfFabZ) which is a trimer of dimers crystallized in a different condition. The catalytic sites of this enzyme are located in deep narrow tunnel-shaped pockets formed at the dimer interface. A histidine residue from one subunit of the dimer and a glutamate residue from the other subunit lining the tunnel form the catalytic dyad in the reported crystal structures. While the position of glutamate remains unaltered in the crystal structure of d-PfFabZ compared to that in h-PfFabZ, the histidine residue takes up an entirely different conformation and moves away from the tunnel leading to a His-Phe cis-trans peptide flip at the histidine residue. In addition, a loop in the vicinity has been observed to undergo a similar flip at a Tyr-Pro peptide bond. These alterations not only prevent the formation of a hexamer but also distort the active site geometry resulting in a dimeric form of FabZ that is incapable of substrate binding. The dimeric stat...Continue Reading

References

Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Sep 1, 1967·Proceedings of the National Academy of Sciences of the United States of America·L R Kass, K Bloch
Jul 12, 1996·Biochimica Et Biophysica Acta·C O Rock, J E Cronan
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Oct 7, 1998·Protein Science : a Publication of the Protein Society·J LiangC Woodward
Oct 15, 1998·Proceedings of the National Academy of Sciences of the United States of America·R F WallerG I McFadden
Aug 25, 1999·Current Opinion in Microbiology·D S RoosB Striepen
Dec 12, 2001·Biochemical and Biophysical Research Communications·M KapoorN Surolia
Feb 9, 2002·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Namita SuroliaAvadhesha Surolia
Oct 9, 2002·Nature·Malcolm J GardnerBart Barrell
Aug 22, 2003·The Journal of Biological Chemistry·Shailendra Kumar SharmaAvadhesha Surolia
Dec 20, 2003·Acta Crystallographica. Section D, Biological Crystallography·Pidugu Lakshmi Swarna MukhiKaza Suguna
Mar 3, 2004·Acta Crystallographica. Section D, Biological Crystallography·Laurent C StoroniRandy J Read
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Aug 19, 2004·The Biochemical Journal·Avadhesha SuroliaNamita Surolia
Sep 17, 2004·The Journal of Biological Chemistry·Matthew S KimberCharles O Rock
Sep 24, 2004·Journal of Molecular Biology·Lakshmi Swarnamukhi PiduguKaza Suguna
Jun 3, 2005·Protein Science : a Publication of the Protein Society·Dirk KostrewaRemo Perozzo

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Citations

Oct 27, 2011·Chemical Reviews·Cyrille Y BottéChristophe Biot
Dec 5, 2012·Chemical Reviews·Jason W Labonte, Craig A Townsend
Oct 12, 2010·Journal of the American Chemical Society·Chiara R ValenzanoDavid E Cane
Aug 24, 2007·Eukaryotic Cell·Jolly Mazumdar, Boris Striepen
May 14, 2010·Journal of the American Chemical Society·Francesco ColizziAndrea Cavalli
Apr 27, 2013·Chemical Reviews·Artur GoraJiri Damborsky
Mar 13, 2009·Biochemical and Biophysical Research Communications·Andrew S KirkpatrickHye-Jeong Yeo
Sep 19, 2007·Current Opinion in Structural Biology·P GayathriM R N Murthy
Nov 23, 2006·International Journal for Parasitology·D J P FergusonC W Roberts
Apr 11, 2012·Chemical Biology & Drug Design·Tabish Qidwai, Feroz Khan
Jun 19, 2010·Drug Development Research·Choukri Ben MamounHenri Vial
Apr 7, 2015·Molecular and Biochemical Parasitology·Melanie J ShearsGeoffrey I McFadden
Jul 11, 2014·The Biochemical Journal·Nyssa Drinkwater, Sheena McGowan
Jul 6, 2013·Progress in Lipid Research·Srinivasan RamakrishnanPeter Bütikofer
Nov 2, 2014·Molecular BioSystems·Joris BeldMichael D Burkart
Feb 14, 2015·Chembiochem : a European Journal of Chemical Biology·Kara FinzelMichael D Burkart
Sep 22, 2010·Bioorganic & Medicinal Chemistry·Deniz TasdemirNéstor M Carballeira

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