6m28 | pdb_00006m28
Sirohydrochlorin nickelochelatase CfbA in complex with Co2+
Structural highlights
FunctionCFBA_METJA Catalyzes the insertion of Co(2+) into sirohydrochlorin as part of the anaerobic pathway to cobalamin biosynthesis. Involved in the biosynthesis of the unique nickel-containing tetrapyrrole coenzyme F430, the prosthetic group of methyl-coenzyme M reductase (MCR), which plays a key role in methanogenesis and anaerobic methane oxidation. Catalyzes the insertion of Ni(2+) into sirohydrochlorin to yield Ni-sirohydrochlorin. Publication Abstract from PubMedThe class II chelatase CfbA catalyzes Ni(2+) insertion into sirohydrochlorin (SHC) to yield the product nickel-sirohydrochlorin (Ni-SHC) during coenzyme F430 biosynthesis. CfbA is an important ancestor of all the class II chelatase family of enzymes, including SirB and CbiK/CbiX, functioning not only as a nickel-chelatase, but also as a cobalt-chelatase in vitro. Thus, CfbA is a key enzyme in terms of diversity and evolution of the chelatases catalyzing formation of metal-SHC-type of cofactors. However, the reaction mechanism of CfbA with Ni(2+) and Co(2+) remains elusive. To understand the structural basis of the underlying mechanisms and evolutionary aspects of the class II chelatases, X-ray crystal structures of Methanocaldococcus jannaschii wild-type CfbA with various ligands, including SHC, Ni(2+), Ni-SHC, and Co(2+) were determined. Further, X-ray crystallographic snapshot analysis captured a unique Ni(2+)-SHC-His intermediate complex and Co-SHC-bound CfbA, which resulted from a more rapid chelatase reaction for Co(2+) than Ni(2+). Meanwhile, an in vitro activity assay confirmed the different reaction rates for Ni(2+) and Co(2+) by CfbA. Based on these structural and functional analyses, the following substrate-SHC-assisted Ni(2+) insertion catalytic mechanism was proposed: Ni(2+) insertion to SHC is promoted by the support of an acetate side chain of SHC. The nickel-sirohydrochlorin formation mechanism of the ancestral class II chelatase CfbA in coenzyme F430 biosynthesis.,Fujishiro T, Ogawa S Chem Sci. 2021 Jan 4;12(6):2172-2180. doi: 10.1039/d0sc05439a. PMID:34163982[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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