The structure of (3R)-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from Pseudomonas aeruginosa.

The Journal of Biological Chemistry
Matthew S KimberCharles O Rock

Abstract

Type II fatty acid biosynthesis systems are essential for membrane formation in bacteria, making the constituent proteins of this pathway attractive targets for antibacterial drug discovery. The third step in the elongation cycle of the type II fatty acid biosynthesis is catalyzed by beta-hydroxyacyl-(acyl carrier protein) (ACP) dehydratase. There are two isoforms. FabZ, which catalyzes the dehydration of (3R)-hydroxyacyl-ACP to trans-2-acyl-ACP, is a universally expressed component of the bacterial type II system. FabA, the second isoform, as has more limited distribution in nature and, in addition to dehydration, also carries out the isomerization of trans-2- to cis-3-decenoyl-ACP as an essential step in unsaturated fatty acid biosynthesis. We report the structure of FabZ from the important human pathogen Pseudomonas aeruginosa at 2.5 A of resolution. PaFabZ is a hexamer (trimer of dimers) with the His/Glu catalytic dyad located within a deep, narrow tunnel formed at the dimer interface. Site-directed mutagenesis experiments showed that the obvious differences in the active site residues that distinguish the FabA and FabZ subfamilies of dehydratases do not account for the unique ability of FabA to catalyze isomerization. Beca...Continue Reading

References

Dec 29, 1967·Biochemical and Biophysical Research Communications·C H BirgeP R Vagelos
Sep 1, 1967·Proceedings of the National Academy of Sciences of the United States of America·L R Kass, K Bloch
Oct 1, 1967·Proceedings of the National Academy of Sciences of the United States of America·D F Silbert, P R Vagelos
May 31, 1996·Biochimica Et Biophysica Acta·J L Harwood
Jul 12, 1996·Biochimica Et Biophysica Acta·C O Rock, J E Cronan
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·P D AdamsA T Brünger
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Dec 5, 1998·The Journal of Biological Chemistry·M M BenningH M Holden
Apr 28, 2001·Journal of Bacteriology·G E SchujmanD de Mendoza
Jun 22, 2001·Acta Crystallographica. Section D, Biological Crystallography·D G Levitt
Jul 24, 2001·Briefings in Bioinformatics·W Kaplan, T G Littlejohn
Sep 7, 2001·Annual Review of Microbiology·J W Campbell, J E Cronan
Oct 10, 2001·Progress in Lipid Research·R J HeathC O Rock
Apr 24, 2002·Biochemical and Biophysical Research Communications·Charles O Rock, Suzanne Jackowski
Sep 19, 2002·The Journal of Biological Chemistry·Hedia MarrakchiCharles O Rock
Dec 25, 2002·Antimicrobial Agents and Chemotherapy·Ross F WallerGeoffrey I McFadden
Apr 12, 2003·Progress in Lipid Research·Stuart SmithAnil K Joshi
Aug 22, 2003·The Journal of Biological Chemistry·Shailendra Kumar SharmaAvadhesha Surolia
Oct 7, 2003·The Journal of Biological Chemistry·Yong-Mei ZhangCharles O Rock
Dec 20, 2003·Acta Crystallographica. Section D, Biological Crystallography·Pidugu Lakshmi Swarna MukhiKaza Suguna
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

❮ Previous
Next ❯

Citations

Aug 25, 2010·Quarterly Reviews of Biophysics·Timm MaierNenad Ban
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
Sep 28, 2007·Natural Product Reports·Stuart Smith, Shiou-Chuan Tsai
Jul 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Alessandra S EustáquioBradley S Moore
Jan 15, 2013·The Journal of Biological Chemistry·Daina ZengPei Zhou
Jun 5, 2010·The Journal of Biological Chemistry·David E Cane
Jun 15, 2005·Annual Review of Biochemistry·Stephen W White Rock
Mar 3, 2007·Annual Review of Biochemistry·Chaitan KhoslaDavid E Cane
Apr 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Brian Douglas AmesShiou-Chuan Tsai
Feb 6, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jun-ya KatoSueharu Horinouchi
Sep 6, 2008·Science·Timm MaierNenad Ban
Dec 20, 2012·Critical Reviews in Biochemistry and Molecular Biology·Wei XuYi Tang
Oct 7, 2008·Journal of Molecular Biology·Takeshi YokoyamaHye-Jeong Yeo
Mar 13, 2009·Biochemical and Biophysical Research Communications·Andrew S KirkpatrickHye-Jeong Yeo
Feb 7, 2015·Biochemical and Biophysical Research Communications·Rupam BiswasAmit Kumar Das
Oct 28, 2008·Journal of Molecular Biology·Adrian Keatinge-Clay
Oct 25, 2008·Current Opinion in Structural Biology·Marc LeibundgutNenad Ban
Nov 10, 2006·Molecular & Cellular Proteomics : MCP·Slovénie PyndiahMarc Bonneu
Mar 10, 2018·Protein Science : a Publication of the Protein Society·Carlos Rullán-LindAbel Baerga-Ortiz
Nov 2, 2014·Molecular BioSystems·Joris BeldMichael D Burkart
Sep 29, 2011·Chembiochem : a European Journal of Chemical Biology·Jeroen S DickschatYuhui Sun
Sep 28, 2006·Chembiochem : a European Journal of Chemical Biology·Tomomi MoriguchiIsao Fujii
Feb 14, 2015·Chembiochem : a European Journal of Chemical Biology·Kara FinzelMichael D Burkart
Jul 22, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·David H Kwan, Frank Schulz
Nov 21, 2018·Organic & Biomolecular Chemistry·Xinqiang Xie, David E Cane

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.