4ex9 | pdb_00004ex9

Crystal structure of the prealnumycin C-glycosynthase AlnA in complex with ribulose 5-phosphate

spinqualitylabelsall models 4ex9, resolution 3.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ex9 is a 1 chain structure with sequence from Streptomyces sp. cm020. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 5RP, CA, CL, EPE Related: 4ex6, 4ex7, 4ex8 Gene: alnA (Streptomyces sp. CM020) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Alnumycin A is an exceptional aromatic polyketide that contains a carbohydrate-like 4'-hydroxy-5'-hydroxymethyl-2',7'-dioxane moiety attached to the aglycone via a carbon-carbon bond. Recently, we have identified the d-ribose-5-phosphate origin of the dioxane unit and demonstrated that AlnA and AlnB are responsible for the overall C-ribosylation reaction. Here, we provide direct evidence that AlnA is a natural C-glycosynthase, which catalyzes the attachment of d-ribose-5-phosphate to prealnumycin by formation of the C(8)-C(1') bond as demonstrated by the structure of the intermediate alnumycin P. This compound is subsequently dephosphorylated by AlnB, an enzyme of the haloacid dehalogenase superfamily. Structure determination of the native trimeric AlnA to 2.1-A resolution revealed a highly globular fold encompassing an alpha/beta/alpha sandwich. The crystal structure of the complex with d-ribose-5-phosphate indicated that the phosphosugar is bound in the open-chain configuration. Identification of residues E29, K86, and K159 near the C-1 carbonyl of the ligand led us to propose that the carbon-carbon bond formation proceeds through a Michael-type addition. Determination of the crystal structure of the monomeric AlnB in the open conformation to 1.25-A resolution showed that the protein consists of core and cap domains. Modeling of alnumycin P inside the cap domain positioned the phosphate group next to a Mg(2+) ion present at the junction of the domains. Mutagenesis data were consistent with the canonical reaction mechanism for this enzyme family revealing the importance of residues D15 and D17 for catalysis. The characterization of the prealnumycin C-ribosylation illustrates an alternative means for attachment of carbohydrates to natural products. Structural basis for C-ribosylation in the alnumycin A biosynthetic pathway.,Oja T, Niiranen L, Sandalova T, Klika KD, Niemi J, Mantsala P, Schneider G, Metsa-Ketela M Proc Natl Acad Sci U S A. 2013 Jan 7. PMID:23297194 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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