1ebl: Difference between revisions

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THE 1.8 A CRYSTAL STRUCTURE AND ACTIVE SITE ARCHITECTURE OF BETA-KETOACYL-[ACYL CARRIER PROTEIN] SYNTHASE III (FABH) FROM ESCHERICHIA COLI

OverviewOverview

Background: beta-Ketoacyl-acyl carrier protein synthase III (FabH) initiates elongation in type II fatty acid synthase systems found in bacteria and plants. FabH is a ubiquitous component of the type II system and is positioned ideally in the pathway to control the production of fatty acids. The elucidation of the structure of FabH is important for the understanding of its regulation by feedback inhibition and its interaction with drugs. Although the structures of two related condensing enzymes are known, the roles of the active-site residues have not been experimentally tested. Results: The 1.8 A crystal structure of FabH was determined using a 12-site selenium multiwavelength anomalous dispersion experiment. The active site (Cys112, His244 and Asn274) is formed by the convergence of two alpha helices and is accessed via a narrow hydrophobic tunnel. Hydrogen-bonding networks that include two tightly bound water molecules fix the positions of His244 and Asn274, which are critical for the decarboxylation and condensation reactions. Surprisingly, the His244-->Ala mutation does not affect the transacylation reaction suggesting that His244 has only a minor influence on the nucleophilicity of Cys112. Conclusions: The histidine and asparagine active-site residues are both required for the decarboxylation step in the condensation reaction. The nucleophilicity of the active-site cysteine is enhanced by the alpha-helix dipole effect, and an oxyanion hole promotes the formation of the tetrahedral transition state.

About this StructureAbout this Structure

1EBL is a Single protein structure of sequence from Escherichia coli with as ligand. Active as Beta-ketoacyl-acyl-carrier-protein synthase I, with EC number 2.3.1.41 Full crystallographic information is available from OCA.

ReferenceReference

The 1.8 A crystal structure and active-site architecture of beta-ketoacyl-acyl carrier protein synthase III (FabH) from escherichia coli., Davies C, Heath RJ, White SW, Rock CO, Structure. 2000 Feb 15;8(2):185-95. PMID:10673437

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-[[Image:1ebl.jpg|left|200px]]<br /><applet load="1ebl" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1ebl.jpg|left|200px]]<br /><applet load="1ebl" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1ebl, resolution 1.8&Aring;" />
 '''THE 1.8 A CRYSTAL STRUCTURE AND ACTIVE SITE ARCHITECTURE OF BETA-KETOACYL-[ACYL CARRIER PROTEIN] SYNTHASE III (FABH) FROM ESCHERICHIA COLI'''<br />
 ==Overview==
-Background: beta-Ketoacyl-acyl carrier protein synthase III (FabH), initiates elongation in type II fatty acid synthase systems found in, bacteria and plants. FabH is a ubiquitous component of the type II system, and is positioned ideally in the pathway to control the production of, fatty acids. The elucidation of the structure of FabH is important for the, understanding of its regulation by feedback inhibition and its interaction, with drugs. Although the structures of two related condensing enzymes are, known, the roles of the active-site residues have not been experimentally, tested. Results: The 1.8 A crystal structure of FabH was determined using, a 12-site selenium multiwavelength anomalous dispersion experiment. The, active site (Cys112, His244 and Asn274) is formed by the convergence of, two alpha helices and is accessed via a narrow hydrophobic tunnel., Hydrogen-bonding networks that include two tightly bound water molecules, fix the positions of His244 and Asn274, which are critical for the, decarboxylation and condensation reactions. Surprisingly, the His244--&gt;Ala, mutation does not affect the transacylation reaction suggesting that, His244 has only a minor influence on the nucleophilicity of Cys112., Conclusions: The histidine and asparagine active-site residues are both, required for the decarboxylation step in the condensation reaction. The, nucleophilicity of the active-site cysteine is enhanced by the alpha-helix, dipole effect, and an oxyanion hole promotes the formation of the, tetrahedral transition state.
+Background: beta-Ketoacyl-acyl carrier protein synthase III (FabH) initiates elongation in type II fatty acid synthase systems found in bacteria and plants. FabH is a ubiquitous component of the type II system and is positioned ideally in the pathway to control the production of fatty acids. The elucidation of the structure of FabH is important for the understanding of its regulation by feedback inhibition and its interaction with drugs. Although the structures of two related condensing enzymes are known, the roles of the active-site residues have not been experimentally tested. Results: The 1.8 A crystal structure of FabH was determined using a 12-site selenium multiwavelength anomalous dispersion experiment. The active site (Cys112, His244 and Asn274) is formed by the convergence of two alpha helices and is accessed via a narrow hydrophobic tunnel. Hydrogen-bonding networks that include two tightly bound water molecules fix the positions of His244 and Asn274, which are critical for the decarboxylation and condensation reactions. Surprisingly, the His244--&gt;Ala mutation does not affect the transacylation reaction suggesting that His244 has only a minor influence on the nucleophilicity of Cys112. Conclusions: The histidine and asparagine active-site residues are both required for the decarboxylation step in the condensation reaction. The nucleophilicity of the active-site cysteine is enhanced by the alpha-helix dipole effect, and an oxyanion hole promotes the formation of the tetrahedral transition state.
 ==About this Structure==
-EBL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with COA as [http://en.wikipedia.org/wiki/ligand ligand]. 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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EBL OCA].
+EBL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=COA:'>COA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EBL OCA].
 ==Reference==
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 [[Category: Single protein]]
 [[Category: Davies, C.]]
-[[Category: Heath, R.J.]]
+[[Category: Heath, R J.]]
-[[Category: Rock, C.O.]]
+[[Category: Rock, C O.]]
-[[Category: White, S.W.]]
+[[Category: White, S W.]]
 [[Category: COA]]
 [[Category: acyltransferase]]
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 [[Category: malonyl coa decarboxylating enzyme]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 13:52:45 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:26:07 2008''