3wy7

Crystal structure of Mycobacterium smegmatis 7-Keto-8-aminopelargonic acid (KAPA) synthase BioF

spinqualitylabelsall models 3wy7, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3wy7 is a 4 chain structure with sequence from Mycolicibacterium smegmatis MC2 155. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BIOF_MYCS2 Publication Abstract from PubMed The biotin biosynthesis pathway is an attractive target for development of novel drugs against mycobacterial pathogens, however there are as yet no suitable inhibitors that target this pathway in mycobacteria. 7-Keto-8-aminopelargonic acid synthase (KAPA synthase, BioF) is the enzyme which catalyzes the first committed step of the biotin synthesis pathway, but both its structure and function in mycobacteria remain unresolved. Here we present the crystal structure of Mycobacterium smegmatis BioF (MsBioF). The structure reveals an incomplete dimer, and the active site organization is similar to, but distinct from Escherichia coli 8-amino-7-oxononanoate synthase (EcAONS), the E. coli homologue of BioF. To investigate the influence of structural characteristics on the function of MsBioF, we deleted bioF in M. smegmatis and confirmed that BioF is required for growth in the absence of exogenous biotin. Based on structural and mutagenesis studies, we confirmed that pyridoxal 5'-phosphate (PLP) binding site residues His129, Lys235 and His200 are essential for MsBioF activity in vivo and residue Glu171 plays an important, but not essential role in MsBioF activity. The N-terminus (residues 1-37) is also essential for MsBioF activity in vivo. The structure and function of MsBioF reported here provides further insights for developing new anti-tuberculosis inhibitors aimed at the biotin synthesis pathway. Structure and function of Mycobacterium smegmatis 7-keto-8-aminopelargonic acid (KAPA) synthase.,Fan S, Li DF, Wang DC, Fleming J, Zhang H, Zhou Y, Zhou L, Zhou J, Chen T, Chen G, Zhang XE, Bi L Int J Biochem Cell Biol. 2014 Nov 18;58C:71-80. doi:, 10.1016/j.biocel.2014.11.006. PMID:25462832 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA