5loq

Publication Abstract from PubMed

Heme biosynthesis in Gram positive bacteria follows a recently described coproporphyrin-dependent pathway with HemQ catalyzing the decarboxylation of coproheme to heme b. Here we present the first crystal structure of a HemQ (homopentameric coproproheme-HemQ from Listeria monocytogenes) at 1.69 A resolution and the conversion of coproheme to heme b followed by UV-vis and resonance Raman spectroscopy as well as mass spectrometry. The ferric 5-coordinated coproheme iron of HemQ is weakly bound by a neutral proximal histidine H174. In the crystal structure of the resting state the distal Q187 (conserved in Firmicutes HemQ) is H-bonded with propionate p2 and the hydrophobic distal cavity lacks solvent water molecules. Two H2 O2 molecules are shown to be necessary for decarboxylation of the propionates p2 and p4 thereby forming the corresponding vinyl groups of heme b. The overall reaction is relatively slow (kcat /KM = 1.8 x 102 M-1 s-1 at pH 7.0) and occurs in a step-wise manner with a three-propionate intermediate. We present the non-covalent interactions between coproheme and the protein and propose a two-step reaction mechanism. Furthermore, the structure of coproheme-HemQ is compared to that of the phylogenetically related heme b-containing chlorite dismutases. This article is protected by copyright. All rights reserved.

Hydrogen peroxide-mediated conversion of coproheme to heme b by HemQ - Lessons from the first crystal structure and kinetic studies.,Hofbauer S, Mlynek G, Milazzo L, Puhringer D, Maresch D, Schaffner I, Furtmuller PG, Smulevich G, Djinovic-Carugo K, Obinger C FEBS J. 2016 Oct 18. doi: 10.1111/febs.13930. PMID:27758026^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.