Conserved hydrogen bonding networks of MitoNEET tune Fe-S cluster binding and structural stability.

ABSTRACT: While its biological function remains unclear, the three-cysteine, one-histidine ligated human [2Fe-2S] cluster containing protein mitoNEET is of interest because of its interaction with the anti-diabetes drug pioglitazone. The mitoNEET [2Fe-2S] cluster demonstrates proton-coupled electron transfer (PCET) and marked cluster instability, which have both been linked to the single His ligand. Highly conserved hydrogen bonding networks, which include the His-87 ligand, exist around the [2Fe-2S] cluster. Through a series of site-directed mutations, PCET of the cluster has been examined, demonstrating that multiple sites of protonation exist in addition to the His ligand, which can influence redox potential. The mutations also demonstrate that while replacement of the His ligand with cysteine re

SUBMITTER: Bak DW 

PROVIDER: S-EPMC3940166 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature