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Common chelatase design in the branched tetrapyrrole pathways of heme and anaerobic cobalamin synthesis

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JournalBiochemistry
DatePublished - 17 Aug 1999
Issue number33
Volume38
Number of pages10
Pages (from-to)10660-10669
Original languageEnglish

Abstract

Prosthetic groups such as heme, chlorophyll, and cobalamin (vitamin B-12) are characterized by their branched biosynthetic pathway and unique metal insertion steps. The metal ion chelatases can be broadly classed either as single-subunit ATP-independent enzymes, such as the anaerobic cobalt chelatase and the protoporphyrin IX (PPIX) ferrochelatase, or as heterotrimeric, ATP-dependent enzymes, such as the Mg chelatase involved in chlorophyll biosynthesis. The X-ray structure of the anaerobic cobalt chelatase from Salmonella typhimurium, CbiK, has been solved to 2.4 Angstrom resolution. Despite a lack of significant amino acid sequence similarity, the protein structure is homologous to that of Bacillus subtilis PPIX ferrochelatase. Both enzymes contain a histidine residue previously identified as the metal ion ligand, but CbiK contains a second histidine in place of the glutamic acid residue identified as a general base in PPM: ferrochelatase. Site-directed mutagenesis has confirmed a role for this histidine and a nearby glutamic acid in cobalt binding, modulating metal ion specificity as well as catalytic efficiency. Contrary to the predicted protoporphyrin binding site in PPIX ferrochelatase, the precorrin-2 binding site in CbiK is clearly defined within a large horizontal cleft between the N- and C-terminal domains. The structural similarity has implications for the understanding of the evolution of this branched biosynthetic pathway.

    Research areas

  • DIRECTED MUTAGENESIS, CRYSTAL-STRUCTURE, ACTIVE-SITE, FERROCHELATASE, BIOSYNTHESIS, VITAMIN-B-12, ENZYME, B-12, IDENTIFICATION, DISTORTION

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