2ix4: Difference between revisions
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==Overview== | ==Overview== | ||
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 ... | 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 Structure== | ==About this Structure== | ||
2IX4 is a | 2IX4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana] with K and 6NA 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] Structure known Active Site: ACA. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2IX4 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: transit peptide]] | [[Category: transit peptide]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:21:34 2007'' | ||
