4zbt | pdb_00004zbt
Streptomyces bingchenggensis aldolase-dehydratase in Schiff base complex with pyruvate
Structural highlights
FunctionPublication Abstract from PubMedThe acetoacetate decarboxylase-like super family (ADCSF) is a group of ~4000 enzymes that, until recently, was thought to be homogenous in terms of the reaction catalyzed. Bioinformatic analysis shows that the ADCSF consists of up to seven families that differ primarily in their active site architectures. The soil-dwelling bacterium Streptomyces bingchenggensis BCW-1 produces an ADCSF enzyme of unknown function that has low (~20%) sequence identity to known acetoacetate decarboxylases (ADCs). This enzyme, Sbi00515, belongs to the MppR-like family of the ADCSF due to its similarity to the mannopeptimycin biosynthetic protein MppR from Streptomyces hygroscopicus. Herein we present steady state kinetic data that show Sbi00515 does not catalyze the decarboxylation of any alpha- or beta-keto acid tested. Rather, we show that Sbi00515 catalyzes the condensation of pyruvate with a number of aldehydes, followed by dehydration of the presumed aldol intermediate. Thus, Sbi00515 is a pyruvate aldolase-dehydratase and not an acetoacetate decarboxylase. We have also determined the X-ray crystal structures of Sbi00515 in complexes with formate and pyruvate. The structures show that the tertiary structure of Sbi00515 is nearly identical to those of both ADC and MppR. The pyruvate complex is trapped as the Schiff base, providing evidence that the Schiff base chemistry that drives the acetoacetate decarboxylases has been co-opted to perform a new function, and that this core chemistry may be conserved across the super family. The structures also suggest possible catalytic roles for several active site residues. Sbi00515, a Protein of Unknown Function from Streptomyces bingchenggensis, Highlights the Functional Versatility of the Acetoacetate Decarboxylase Scaffold.,Mueller LS, Hoppe RW, Ochsenwald JM, Berndt RT, Severin GB, Schwabacher AW, Silvaggi NR Biochemistry. 2015 Jun 3. PMID:26039798[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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