6xuc

Structure of coproheme decarboxylase from Corynebacterium diphteriae in complex with coproheme

spinqualitylabelsall models 6xuc, resolution 1.87Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6xuc is a 5 chain structure with sequence from Corynebacterium diphtheriae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8702Å Ligands: FEC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6NGV6_CORDI Involved in coproporphyrin-dependent heme b biosynthesis. Catalyzes the decarboxylation of Fe-coproporphyrin III (coproheme) to heme b (protoheme IX), the last step of the pathway. The reaction occurs in a stepwise manner with a three-propionate intermediate.[HAMAP-Rule:MF_02244] Publication Abstract from PubMed Coproheme decarboxylases (ChdCs) catalyze the final step in heme b biosynthesis of monoderm and some diderm bacteria. In this reaction, coproheme is converted to heme b via monovinyl monopropionate deuteroheme (MMD) in two consecutive decarboxylation steps. In Firmicutes decarboxylation of propionates 2 and 4 of coproheme depend on hydrogen peroxide and the presence of a catalytic tyrosine. Here we demonstrate that ChdCs from Actinobacteria are unique in using a histidine (H118 in ChdC from Corynebacterium diphtheriae, CdChdC) as a distal base in addition to the redox-active tyrosine (Y135). We present the X-ray crystal structures of coproheme-CdChdC and MMD-CdChdC, which clearly show (i) differences in the active site architecture between Firmicutes and Actinobacteria and (ii) rotation of the redox-active reaction intermediate (MMD) after formation of the vinyl group at position 2. Distal H118 is shown to catalyze the heterolytic cleavage of hydrogen peroxide (k app = (4.90 +/- 1.25) x 10(4) M(-1) s(-1)). The resulting Compound I is rapidly converted to a catalytically active Compound I* (oxoiron(IV) Y135(*)) that initiates the radical decarboxylation reactions. As a consequence of the more efficient Compound I formation, actinobacterial ChdCs exhibit a higher catalytic efficiency in comparison to representatives from Firmicutes. On the basis of the kinetic data of wild-type CdChdC and the variants H118A, Y135A, and H118A/Y135A together with high-resolution crystal structures and molecular dynamics simulations, we present a molecular mechanism for the hydrogen peroxide dependent conversion of coproheme via MMD to heme b and discuss differences between ChdCs from Actinobacteria and Firmicutes. Actinobacterial Coproheme Decarboxylases Use Histidine as a Distal Base to Promote Compound I Formation.,Michlits H, Lier B, Pfanzagl V, Djinovic-Carugo K, Furtmuller PG, Oostenbrink C, Obinger C, Hofbauer S ACS Catal. 2020 May 15;10(10):5405-5418. doi: 10.1021/acscatal.0c00411. Epub 2020, Apr 9. PMID:32440366 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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