1b4k: Difference between revisions

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HIGH RESOLUTION CRYSTAL STRUCTURE OF A MG2-DEPENDENT 5-AMINOLEVULINIC ACID DEHYDRATASE

OverviewOverview

Common to the biosynthesis of all known tetrapyrroles is the condensation of two molecules of 5-aminolevulinic acid to the pyrrole porphobilinogen catalyzed by the enzyme porphobilinogen synthase (PBGS). Two major classes of PBGS are known. Zn2+-dependent PBGSs are found in mammals, yeast and some bacteria including Escherichia coli, while Mg2+-dependent PBGSs are present mainly in plants and other bacteria. The crystal structure of the Mg2+-dependent PBGS from the human pathogen Pseudomonas aeruginosa in complex with the competitive inhibitor levulinic acid (LA) solved at 1.67 A resolution shows a homooctameric enzyme that consists of four asymmetric dimers. The monomers in each dimer differ from each other by having a "closed" and an "open" active site pocket. In the closed subunit, the active site is completely shielded from solvent by a well-defined lid that is partially disordered in the open subunit. A single molecule of LA binds to a mainly hydrophobic pocket in each monomer where it is covalently attached via a Schiff base to an active site lysine residue. Whereas no metal ions are found in the active site of both monomers, a single well-defined and highly hydrated Mg2+is present only in the closed form about 14 A away from the Schiff base forming nitrogen atom of the active site lysine. We conclude that the observed differences in the active sites of both monomers might be induced by Mg2+-binding to this remote site and propose a structure-based mechanism for this allosteric Mg2+in rate enhancement.

About this StructureAbout this Structure

1B4K is a Single protein structure of sequence from Pseudomonas aeruginosa with , and as ligands. Active as Porphobilinogen synthase, with EC number 4.2.1.24 Full crystallographic information is available from OCA.

ReferenceReference

High resolution crystal structure of a Mg2+-dependent porphobilinogen synthase., Frankenberg N, Erskine PT, Cooper JB, Shoolingin-Jordan PM, Jahn D, Heinz DW, J Mol Biol. 1999 Jun 11;289(3):591-602. PMID:10356331

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-[[Image:1b4k.gif|left|200px]]<br /><applet load="1b4k" size="450" color="white" frame="true" align="right" spinBox="true"
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 caption="1b4k, resolution 1.67&Aring;" />
 '''HIGH RESOLUTION CRYSTAL STRUCTURE OF A MG2-DEPENDENT 5-AMINOLEVULINIC ACID DEHYDRATASE'''<br />
 ==Overview==
-Common to the biosynthesis of all known tetrapyrroles is the condensation, of two molecules of 5-aminolevulinic acid to the pyrrole porphobilinogen, catalyzed by the enzyme porphobilinogen synthase (PBGS). Two major classes, of PBGS are known. Zn2+-dependent PBGSs are found in mammals, yeast and, some bacteria including Escherichia coli, while Mg2+-dependent PBGSs are, present mainly in plants and other bacteria. The crystal structure of the, Mg2+-dependent PBGS from the human pathogen Pseudomonas aeruginosa in, complex with the competitive inhibitor levulinic acid (LA) solved at 1.67, A resolution shows a homooctameric enzyme that consists of four asymmetric, dimers. The monomers in each dimer differ from each other by having a, "closed" and an "open" active site pocket. In the closed subunit, the, active site is completely shielded from solvent by a well-defined lid that, is partially disordered in the open subunit. A single molecule of LA binds, to a mainly hydrophobic pocket in each monomer where it is covalently, attached via a Schiff base to an active site lysine residue. Whereas no, metal ions are found in the active site of both monomers, a single, well-defined and highly hydrated Mg2+is present only in the closed form, about 14 A away from the Schiff base forming nitrogen atom of the active, site lysine. We conclude that the observed differences in the active sites, of both monomers might be induced by Mg2+-binding to this remote site and, propose a structure-based mechanism for this allosteric Mg2+in rate, enhancement.
+Common to the biosynthesis of all known tetrapyrroles is the condensation of two molecules of 5-aminolevulinic acid to the pyrrole porphobilinogen catalyzed by the enzyme porphobilinogen synthase (PBGS). Two major classes of PBGS are known. Zn2+-dependent PBGSs are found in mammals, yeast and some bacteria including Escherichia coli, while Mg2+-dependent PBGSs are present mainly in plants and other bacteria. The crystal structure of the Mg2+-dependent PBGS from the human pathogen Pseudomonas aeruginosa in complex with the competitive inhibitor levulinic acid (LA) solved at 1.67 A resolution shows a homooctameric enzyme that consists of four asymmetric dimers. The monomers in each dimer differ from each other by having a "closed" and an "open" active site pocket. In the closed subunit, the active site is completely shielded from solvent by a well-defined lid that is partially disordered in the open subunit. A single molecule of LA binds to a mainly hydrophobic pocket in each monomer where it is covalently attached via a Schiff base to an active site lysine residue. Whereas no metal ions are found in the active site of both monomers, a single well-defined and highly hydrated Mg2+is present only in the closed form about 14 A away from the Schiff base forming nitrogen atom of the active site lysine. We conclude that the observed differences in the active sites of both monomers might be induced by Mg2+-binding to this remote site and propose a structure-based mechanism for this allosteric Mg2+in rate enhancement.
 ==About this Structure==
-B4K is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with SO4, MG and LEA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Porphobilinogen_synthase Porphobilinogen synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.24 4.2.1.24] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1B4K OCA].
+B4K is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=LEA:'>LEA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Porphobilinogen_synthase Porphobilinogen synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.24 4.2.1.24] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B4K OCA].
 ==Reference==
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 [[Category: Single protein]]
 [[Category: Frankenberg, N.]]
-[[Category: Heinz, D.W.]]
+[[Category: Heinz, D W.]]
 [[Category: Jahn, D.]]
 [[Category: LEA]]
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 [[Category: magnesium]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 11:21:18 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:51:22 2008''