Publication Abstract from PubMed
The isobacteriochlorin heme d1 serves as an essential cofactor in the cytochrome cd1 nitrite reductase NirS which plays an important role for denitrification. During the biosynthesis of heme d1 the enzyme siroheme decarboxylase catalyzes the conversion of siroheme to 12,18-didecarboxysiroheme. This enzyme was discovered recently (Bali et al. (2011) Proc. Natl. Acad. Sci. USA 108, 18260-5) and is only scarcely characterized. Here, we present the crystal structure of the siroheme decarboxylase from Hydrogenobacter thermophilus representing the first three-dimensional structure for this type of enzyme. The overall structure strikingly resembles those of transcriptional regulators of the Lrp/AsnC-family. Moreover, the structure of the enzyme in complex with a substrate analog reveals first insights into its active site architecture. Through site-directed mutagenesis and subsequent biochemical characterization of the enzyme variants two conserved histidine residues within the active site are identified to be involved in substrate binding and catalysis. Based on our results we propose a potential catalytic mechanism for the enzymatic reaction catalyzed by the siroheme decarboxylase.
The crystal structure of siroheme decarboxylase in complex with iron-uroporphyrin III reveals two essential histidine residues.,Haufschildt K, Schmelz S, Kriegler TM, Neumann A, Streif J, Arai H, Heinz DW, Layer G J Mol Biol. 2014 Jul 29. pii: S0022-2836(14)00369-6. doi:, 10.1016/j.jmb.2014.07.021. PMID:25083922[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
