A Case of Iron Poisoning

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Science  27 Jul 2007:
Vol. 317, Issue 5837, pp. 429
DOI: 10.1126/science.317.5837.429b

In order to carry out redox reactions on small diatomic gases (such as H2 and N2), enzymes enlist the help of metal atoms, often grouping them into clusters and decorating them with nonprotein ligands. The [NiFe] hydrogenase offers a case in point; within the Ni-Fe cluster at the active site, the iron atom binds two molecules of cyanide and one of carbon monoxide. Previously, the hydrogenase maturation protein HypF has been shown to transfer a carbamoyl group to a cysteine residue of HypE, which then dehydrates it in situ to generate a thiocyanate (enzyme-SCN).

Watanabe et al. have solved the crystal structures of the proteins HypC, HypD, and HypE, which together append the two cyanide moieties to the iron atom—subsequently, a CO is added and the Fe(CN)2(CO) subassembly is cemented into the large subunit of the hydrogenase before the Ni atom is inserted. They propose that upon binding of HypE to a HypC-HypD complex, a series of thioldisulfide exchanges occurs. These reactions transfer the CN group from the cysteine of HypE onto the iron atom, which is jointly coordinated by cysteine and histidine residues contributed by HypC and HypD; repeating these steps with a second charged HypE serves to add the second CN ligand. HypD contains its own [4Fe-4S] cluster, which acts catalytically, rather than constitutionally, in facilitating the cysteine redox cascade. — GJC

Mol. Cell 27, 29 (2007).

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