2iwz: Difference between revisions

Revision as of 08:00, 4 May 2008

HUMAN MITOCHONDRIAL BETA-KETOACYL ACP SYNTHASE COMPLEXED WITH HEXANOIC ACID

OverviewOverview

Two distinct ways of organizing fatty acid biosynthesis exist: the multifunctional type I fatty acid synthase (FAS) of mammals, fungi, and lower eukaryotes with activities residing on one or two polypeptides; and the dissociated type II FAS of prokaryotes, plastids, and mitochondria with individual activities encoded by discrete genes. The beta-ketoacyl [ACP] synthase (KAS) moiety of the mitochondrial FAS (mtKAS) is targeted by the antibiotic cerulenin and possibly by the other antibiotics inhibiting prokaryotic KASes: thiolactomycin, platensimycin, and the alpha-methylene butyrolactone, C75. The high degree of structural similarity between mitochondrial and prokaryotic KASes complicates development of novel antibiotics targeting prokaryotic KAS without affecting KAS domains of cytoplasmic FAS. KASes catalyze the C(2) fatty acid elongation reaction using either a Cys-His-His or Cys-His-Asn catalytic triad. Three KASes with different substrate specificities participate in synthesis of the C(16) and C(18) products of prokaryotic FAS. By comparison, mtKAS carries out all elongation reactions in the mitochondria. We present the X-ray crystal structures of the Cys-His-His-containing human mtKAS and its hexanoyl complex plus the hexanoyl complex of the plant mtKAS from Arabidopsis thaliana. The structures explain (1) the bimodal (C(6) and C(10)-C(12)) substrate preferences leading to the C(8) lipoic acid precursor and long chains for the membranes, respectively, and (2) the low cerulenin sensitivity of the human enzyme; and (3) reveal two different potential acyl-binding-pocket extensions. Rearrangements taking place in the active site, including subtle changes in the water network, indicate a change in cooperativity of the active-site histidines upon primer binding.

About this StructureAbout this Structure

2IWZ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structure of the human beta-ketoacyl [ACP] synthase from the mitochondrial type II fatty acid synthase., Christensen CE, Kragelund BB, von Wettstein-Knowles P, Henriksen A, Protein Sci. 2007 Feb;16(2):261-72. PMID:17242430 Page seeded by OCA on Sun May 4 08:00:52 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2iwz.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2iwz |SIZE=350|CAPTION= <scene name='initialview01'>2iwz</scene>, resolution 1.65&Aring;
+The line below this paragraph, containing "STRUCTURE_2iwz", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Nh4+Binding+Site+For+Chain+A'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=6NA:HEXANOIC+ACID'>6NA</scene>, <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-ketoacyl-acyl-carrier-protein_synthase_I Beta-ketoacyl-acyl-carrier-protein synthase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.41 2.3.1.41] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2iwz|  PDB=2iwz  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2iwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iwz OCA], [http://www.ebi.ac.uk/pdbsum/2iwz PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2iwz RCSB]</span>
-}}
 '''HUMAN MITOCHONDRIAL BETA-KETOACYL ACP SYNTHASE COMPLEXED WITH HEXANOIC ACID'''
@@ Line 30: / Line 27: @@
 [[Category: Kragelund, B.]]
 [[Category: Wettstein-Knowles, P Von.]]
-[[Category: acyltransferase]]
+[[Category: Acyltransferase]]
-[[Category: beta-ketoacyl acp synthase]]
+[[Category: Beta-ketoacyl acp synthase]]
-[[Category: cerulenin]]
+[[Category: Cerulenin]]
-[[Category: claisen condensation]]
+[[Category: Claisen condensation]]
-[[Category: fatty acid biosynthesis]]
+[[Category: Fatty acid biosynthesis]]
-[[Category: fatty acid synthesis]]
+[[Category: Fatty acid synthesis]]
-[[Category: homo sapien]]
+[[Category: Homo sapien]]
-[[Category: ka]]
+[[Category: Ka]]
-[[Category: lipid synthesis]]
+[[Category: Lipid synthesis]]
-[[Category: mitochondria]]
+[[Category: Mitochondria]]
-[[Category: mitochondrion]]
+[[Category: Mitochondrion]]
-[[Category: transferase]]
+[[Category: Transferase]]
-[[Category: transit peptide]]
+[[Category: Transit peptide]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 08:00:52 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:49:50 2008''