1b4k
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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 SO4, MG and LEA 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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