Structural highlights
Function
[BIOF_ECOLI] Catalyzes the decarboxylative condensation of pimeloyl-[acyl-carrier protein] and L-alanine to produce 8-amino-7-oxononanoate (AON), [acyl-carrier protein], and carbon dioxide. Can also use pimeloyl-CoA instead of pimeloyl-ACP as substrate, but it is believed that pimeloyl-ACP rather than pimeloyl-CoA is the physiological substrate of BioF.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
8-Amino-7-oxononanoate synthase (or 8-amino-7-ketopelargonate synthase; EC 2.3.1.47; AONS) catalyses the decarboxylative condensation of l-alanine and pimeloyl-CoA in the first committed step of biotin biosynthesis. We have cloned, over-expressed and purified AONS from Escherichia coli and determined the crystal structures of the apo and PLP-bound forms of the enzyme. The protein is a symmetrical homodimer with a tertiary structure and active site organisation similar to, but distinct from, those of other PLP-dependent enzymes whose three-dimensional structures are known. The critical PLP-binding lysine of AONS is located at the end of a deep cleft that allows access of the pantothenate arm of pimeloyl-CoA. A cluster of positively charged residues at the entrance to this cleft forms a putative diphosphate binding site for CoA. The structure of E. coli AONS enables identification of the key residues of the PLP-binding site and thus provides a framework with which to understand the biochemical mechanism, which is similar to that catalysed by 5-aminolevulinate synthase and two other alpha-oxoamine synthases. Although AONS has a low overall sequence similarity with the catalytic domains of other alpha-oxoamine synthases, the structure reveals the regions of significant identity to be functionally important. This suggests that the organisation of the conserved catalytic residues in the active site is similar for all enzymes of this sub-class of PLP-dependent enzymes and they share a common mechanism. Knowledge of the three-dimensional structure of AONS will enable characterisation of the structural features of this enzyme sub-family that are responsible for this important type of reaction.
The crystal structure of 8-amino-7-oxononanoate synthase: a bacterial PLP-dependent, acyl-CoA-condensing enzyme.,Alexeev D, Alexeeva M, Baxter RL, Campopiano DJ, Webster SP, Sawyer L J Mol Biol. 1998 Nov 27;284(2):401-19. PMID:9813126[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin S, Hanson RE, Cronan JE. Biotin synthesis begins by hijacking the fatty acid synthetic pathway. Nat Chem Biol. 2010 Sep;6(9):682-8. doi: 10.1038/nchembio.420. Epub 2010 Aug 8. PMID:20693992 doi:http://dx.doi.org/10.1038/nchembio.420
- ↑ Alexeev D, Alexeeva M, Baxter RL, Campopiano DJ, Webster SP, Sawyer L. The crystal structure of 8-amino-7-oxononanoate synthase: a bacterial PLP-dependent, acyl-CoA-condensing enzyme. J Mol Biol. 1998 Nov 27;284(2):401-19. PMID:9813126 doi:http://dx.doi.org/10.1006/jmbi.1998.2086
