2q2x
From Proteopedia
(New page: 200px<br /><applet load="2q2x" size="350" color="white" frame="true" align="right" spinBox="true" caption="2q2x, resolution 2.000Å" /> '''Crystal Structure o...) |
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caption="2q2x, resolution 2.000Å" /> | caption="2q2x, resolution 2.000Å" /> | ||
'''Crystal Structure of the ECH2 decarboxylase domain of CurF from Lyngbya majuscula'''<br /> | '''Crystal Structure of the ECH2 decarboxylase domain of CurF from Lyngbya majuscula'''<br /> | ||
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| + | ==Overview== | ||
| + | Curacin A is a mixed polyketide/nonribosomal peptide possessing, anti-mitotic and anti-proliferative activity. In the biosynthesis of, curacin A, the N-terminal domain of the CurF multifunctional protein, catalyzes decarboxylation of 3-methylglutaconyl-acyl carrier protein (ACP), to 3-methylcrotonyl-ACP, the postulated precursor of the cyclopropane ring, of curacin A. This decarboxylase is encoded within an "HCS cassette" that, is used by several other polyketide biosynthetic systems to generate, chemical diversity by introduction of a beta-branch functional group to, the natural product. The crystal structure of the CurF N-terminal ECH(2), domain establishes that the protein is a crotonase superfamily member., Ala(78) and Gly(118) form an oxyanion hole in the active site that, includes only three polar side chains as potential catalytic residues., Site-directed mutagenesis and a biochemical assay established critical, functions for His(240) and Lys(86), whereas Tyr(82) was nonessential. A, decarboxylation mechanism is proposed in which His(240) serves to, stabilize the substrate carboxylate and Lys(86) donates a proton to C-4 of, the acyl-ACP enolate intermediate to form the Delta(2) unsaturated, isopentenoyl-ACP product. The CurF ECH(2) domain showed a 20-fold, selectivity for ACP-over CoA-linked substrates. Specificity for ACP-linked, substrates has not been reported for any other crotonase superfamily, decarboxylase. Tyr(73) may select against CoA-linked substrates by, blocking a contact of Arg(38) with the CoA adenosine 5'-phosphate. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2Q2X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lyngbya_majuscula Lyngbya majuscula] with <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q2X OCA]. | + | 2Q2X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lyngbya_majuscula Lyngbya majuscula] with <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Sites: <scene name='pdbsite=AC1:Gol Binding Site For Residue A 3287'>AC1</scene> and <scene name='pdbsite=AC2:Gol Binding Site For Residue A 3288'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q2X OCA]. |
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| + | ==Reference== | ||
| + | Crystal structure of the ECH2 catalytic domain of CurF from Lyngbya majuscula. Insights into a decarboxylase involved in polyketide chain beta-branching., Geders TW, Gu L, Mowers JC, Liu H, Gerwick WH, Hakansson K, Sherman DH, Smith JL, J Biol Chem. 2007 Dec 7;282(49):35954-63. Epub 2007 Oct 10. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17928301 17928301] | ||
[[Category: Lyngbya majuscula]] | [[Category: Lyngbya majuscula]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: lyase]] | [[Category: lyase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 31 10:57:49 2008'' |
Revision as of 08:57, 31 January 2008
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Crystal Structure of the ECH2 decarboxylase domain of CurF from Lyngbya majuscula
Overview
Curacin A is a mixed polyketide/nonribosomal peptide possessing, anti-mitotic and anti-proliferative activity. In the biosynthesis of, curacin A, the N-terminal domain of the CurF multifunctional protein, catalyzes decarboxylation of 3-methylglutaconyl-acyl carrier protein (ACP), to 3-methylcrotonyl-ACP, the postulated precursor of the cyclopropane ring, of curacin A. This decarboxylase is encoded within an "HCS cassette" that, is used by several other polyketide biosynthetic systems to generate, chemical diversity by introduction of a beta-branch functional group to, the natural product. The crystal structure of the CurF N-terminal ECH(2), domain establishes that the protein is a crotonase superfamily member., Ala(78) and Gly(118) form an oxyanion hole in the active site that, includes only three polar side chains as potential catalytic residues., Site-directed mutagenesis and a biochemical assay established critical, functions for His(240) and Lys(86), whereas Tyr(82) was nonessential. A, decarboxylation mechanism is proposed in which His(240) serves to, stabilize the substrate carboxylate and Lys(86) donates a proton to C-4 of, the acyl-ACP enolate intermediate to form the Delta(2) unsaturated, isopentenoyl-ACP product. The CurF ECH(2) domain showed a 20-fold, selectivity for ACP-over CoA-linked substrates. Specificity for ACP-linked, substrates has not been reported for any other crotonase superfamily, decarboxylase. Tyr(73) may select against CoA-linked substrates by, blocking a contact of Arg(38) with the CoA adenosine 5'-phosphate.
About this Structure
2Q2X is a Single protein structure of sequence from Lyngbya majuscula with as ligand. Known structural/functional Sites: and . Full crystallographic information is available from OCA.
Reference
Crystal structure of the ECH2 catalytic domain of CurF from Lyngbya majuscula. Insights into a decarboxylase involved in polyketide chain beta-branching., Geders TW, Gu L, Mowers JC, Liu H, Gerwick WH, Hakansson K, Sherman DH, Smith JL, J Biol Chem. 2007 Dec 7;282(49):35954-63. Epub 2007 Oct 10. PMID:17928301
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