1mly

Crystal Structure of 7,8-Diaminopelargonic Acid Synthase in complex with the cis isomer of amiclenomycin

spinqualitylabelsall models 1mly, resolution 1.81Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1mly is a 2 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACZ, NA, PLP Related: 1qj5, 1dty, 1qj3, 1mgv, 1mlz Gene: bioA ("Bacillus coli" Migula 1895) Activity: Adenosylmethionine--8-amino-7-oxononanoate transaminase, with EC number 2.6.1.62 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [BIOA_ECOLI] Catalyzes the transfer of the alpha-amino group from S-adenosyl-L-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). It is the only animotransferase known to utilize SAM as an amino donor. 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 The antibiotic amiclenomycin blocks the biosynthesis of biotin by inhibiting the pyridoxal-phosphate-dependent enzyme diaminopelargonic acid synthase. Inactivation of the enzyme is stereoselective, i.e. the cis isomer of amiclenomycin is a potent inhibitor, whereas the trans isomer is much less reactive. The crystal structure of the complex of the holoenzyme and amiclenomycin at 1.8 A resolution reveals that the internal aldimine linkage between the cofactor and the side chain of the catalytic residue Lys-274 is broken. Instead, a covalent bond is formed between the 4-amino nitrogen of amiclenomycin and the C4' carbon atom of pyridoxal-phosphate. The electron density for the bound inhibitor suggests that aromatization of the cyclohexadiene ring has occurred upon formation of the covalent adduct. This process could be initiated by proton abstraction at the C4 carbon atom of the cyclohexadiene ring, possibly by the proximal side chain of Lys-274, leading to the tautomer Schiff base followed by the removal of the second allylic hydrogen. The carboxyl tail of the amiclenomycin moiety forms a salt link to the conserved residue Arg-391 in the substrate-binding site. Modeling suggests steric hindrance at the active site as the determinant of the weak inhibiting potency of the trans isomer. Structural basis for the inhibition of the biosynthesis of biotin by the antibiotic amiclenomycin.,Sandmark J, Mann S, Marquet A, Schneider G J Biol Chem. 2002 Nov 8;277(45):43352-8. Epub 2002 Sep 5. PMID:12218056 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 7%2C8-diaminopelargonic acid synthetase

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