IPR007398 Proteins, all bacterian, Pimeloyl-ACP methyl esterase BioG DUF452. Haemophilus influenzae pimeloyl-acyl carrier protein (ACP) methyl esterase BioG that lack significant sequence identity with other isofunctional forms of this enzyme found in other bacteria (e.g. Escherichia coli BioH or Helicobacter pylori BioV) Shi et al. (previously named DUF_452
Title: Expression and Activity of the BioH Esterase of Biotin Synthesis is Independent of Genome Context Cao X, Zhu L, Hu Z, Cronan JE Ref: Sci Rep, 7:2141, 2017 : PubMed
BioH is an alpha/beta-hydrolase required for synthesis of the pimelate moiety of biotin in diverse bacteria. The bioH gene is found in different genomic contexts. In some cases (e.g., Escherichia coli) the gene is not located within a biotin synthetic operon and its transcription is not coregulated with the other biotin synthesis genes. In other genomes such as Pseudomonas aeruginosa the bioH gene is within a biotin synthesis operon and its transcription is coregulated with the other biotin operon genes. The esterases of pimelate moiety synthesis show remarkable genomic plasticity in that in some biotin operons bioH is replaced by other alpha/ss hydrolases of diverse sequence. The "wild card" nature of these enzymes led us to compare the paradigm "freestanding" E. coli BioH with the operon-encoded P. aeruginosa BioH. We hypothesized that the operon-encoded BioH might differ in its expression level and/or activity from the freestanding BioH gene. We report this is not the case. The two BioH proteins show remarkably similar hydrolase activities and substrate specificity. Moreover, Pseudomonas aeruginosa BioH is more highly expressed than E. coli BioH. Despite the enzymatic similarities of the two BioH proteins, bioinformatics analysis places the freestanding and operon-encoded BioH proteins into distinct clades.
Title: A Biotin Biosynthesis Gene Restricted to Helicobacter Bi H, Zhu L, Jia J, Cronan JE Ref: Sci Rep, 6:21162, 2016 : PubMed
In most bacteria the last step in synthesis of the pimelate moiety of biotin is cleavage of the ester bond of pimeloyl-acyl carrier protein (ACP) methyl ester. The paradigm cleavage enzyme is Escherichia coli BioH which together with the BioC methyltransferase allows synthesis of the pimelate moiety by a modified fatty acid biosynthetic pathway. Analyses of the extant bacterial genomes showed that bioH is absent from many bioC-containing bacteria and is replaced by other genes. Helicobacter pylori lacks a gene encoding a homologue of the known pimeloyl-ACP methyl ester cleavage enzymes suggesting that it encodes a novel enzyme that cleaves this intermediate. We isolated the H. pylori gene encoding this enzyme, bioV, by complementation of an E. coli bioH deletion strain. Purified BioV cleaved the physiological substrate, pimeloyl-ACP methyl ester to pimeloyl-ACP by use of a catalytic triad, each member of which was essential for activity. The role of BioV in biotin biosynthesis was demonstrated using a reconstituted in vitro desthiobiotin synthesis system. BioV homologues seem the sole pimeloyl-ACP methyl ester esterase present in the Helicobacter species and their occurrence only in H. pylori and close relatives provide a target for development of drugs to specifically treat Helicobacter infections.
Title: An Atypical alpha/beta-Hydrolase Fold Revealed in the Crystal Structure of Pimeloyl-Acyl Carrier Protein Methyl Esterase BioG from Haemophilus influenzae Shi J, Cao X, Chen Y, Cronan JE, Guo Z Ref: Biochemistry, 55:6705, 2016 : PubMed
Pimeloyl-acyl carrier protein (ACP) methyl esterase is an alpha/beta-hydrolase that catalyzes the last biosynthetic step of pimeloyl-ACP, a key intermediate in biotin biosynthesis. Intriguingly, multiple nonhomologous isofunctional forms of this enzyme that lack significant sequence identity are present in diverse bacteria. One such esterase, Escherichia coli BioH, has been shown to be a typical alpha/beta-hydrolase fold enzyme. To gain further insights into the role of this step in biotin biosynthesis, we have determined the crystal structure of another widely distributed pimeloyl-ACP methyl esterase, Haemophilus influenzae BioG, at 1.26 A. The BioG structure is similar to the BioH structure and is composed of an alpha-helical lid domain and a core domain that contains a central seven-stranded beta-pleated sheet. However, four of the six alpha-helices that flank both sides of the BioH core beta-sheet are replaced with long loops in BioG, thus forming an unusual alpha/beta-hydrolase fold. This structural variation results in a significantly decreased thermal stability of the enzyme. Nevertheless, the lid domain and the residues at the lid-core interface are well conserved between BioH and BioG, in which an analogous hydrophobic pocket for pimelate binding as well as similar ionic interactions with the ACP moiety are retained. Biochemical characterization of site-directed mutants of the residues hypothesized to interact with the ACP moiety supports a similar substrate interaction mode for the two enzymes. Consequently, these enzymes package the identical catalytic function under a considerably different protein surface.
Other Papers
No structure scheme yet for this family
Structures in BioG_Pimeloyl-ACP-methyl-esterase family (2)
