2iwz: Difference between revisions

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Revision as of 18:34, 20 March 2008

File:2iwz.jpg

, resolution 1.65Å

Sites:

Ligands:

and

Activity:

Beta-ketoacyl-acyl-carrier-protein synthase I, with EC number 2.3.1.41

Coordinates:

save as pdb, mmCIF, xml

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 Thu Mar 20 17:34:31 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]]<br /><applet load="2iwz" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2iwz.jpg|left|200px]]
-caption="2iwz, resolution 1.65&Aring;" />
-'''HUMAN MITOCHONDRIAL BETA-KETOACYL ACP SYNTHASE COMPLEXED WITH HEXANOIC ACID'''<br />
+ {{Structure
+|PDB= 2iwz |SIZE=350|CAPTION= <scene name='initialview01'>2iwz</scene>, resolution 1.65&Aring;
+|SITE= <scene name='pdbsite=AC1:Nh4+Binding+Site+For+Chain+A'>AC1</scene>
+|LIGAND= <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene> and <scene name='pdbligand=6NA:HEXANOIC ACID'>6NA</scene>
+|ACTIVITY= [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]
+|GENE=
+}}
+'''HUMAN MITOCHONDRIAL BETA-KETOACYL ACP SYNTHASE COMPLEXED WITH HEXANOIC ACID'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-IWZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NH4:'>NH4</scene> and <scene name='pdbligand=6NA:'>6NA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:Nh4+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IWZ OCA].
+IWZ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IWZ OCA].
 ==Reference==
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17242430 17242430]
+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:[http://www.ncbi.nlm.nih.gov/pubmed/17242430 17242430]
 [[Category: Beta-ketoacyl-acyl-carrier-protein synthase I]]
 [[Category: Homo sapiens]]
@@ Line 26: / Line 35: @@
 [[Category: fatty acid biosynthesis]]
 [[Category: fatty acid synthesis]]
-[[Category: homo sapiens]]
+[[Category: homo sapien]]
-[[Category: kas]]
+[[Category: ka]]
 [[Category: lipid synthesis]]
 [[Category: mitochondria]]
@@ Line 34: / Line 43: @@
 [[Category: transit peptide]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:56:52 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:34:31 2008''