ArticleProceedings of the National Academy of Sciences of the United States of America2013
Allosteric control in a metalloprotein dramatically alters function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Predicting Metalloprotein Redox Potentials with Machine Learning: A Focus on Iron-Sulfur Systems.Journal of chemical information and modeling · 2025Article
- Predicting Iron-Sulfur Cluster Redox Potentials: A Simple Model Derived from Protein Structures.ACS omega · 2025Article
- Increasing the OACS catalysis · 2023Article
- An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters.Communications biology · 2022Article
- The two redox states of the human NEET proteins' [2Fe-2S] clusters.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2021Article
- NRVS and DFT of MitoNEET: Understanding the Special Vibrational Structure of a [2Fe-2S] Cluster with (Cys)Biochemistry · 2021Article
- Redox-dependent gating of VDAC by mitoNEET.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Uncovering the molecular mechanisms behind disease-associated leptin variants.The Journal of biological chemistry · 2018Article
- The unique fold and lability of the [2Fe-2S] clusters of NEET proteins mediate their key functions in health and disease.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Review
- Structure of the human monomeric NEET protein MiNT and its role in regulating iron and reactive oxygen species in cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Molecular Dynamics Simulations of the [2Fe-2S] Cluster-Binding Domain of NEET Proteins Reveal Key Molecular Determinants That Induce Their Cluster Transfer/Release.The journal of physical chemistry. B · 2017Article
- Flavin nucleotides act as electron shuttles mediating reduction of the [2Fe-2S] clusters in mitochondrial outer membrane protein mitoNEET.Free radical biology & medicine · 2017Article
- Pierced Lasso Bundles are a new class of knot-like motifs.PLoS computational biology · 2014Article
- Utilizing a dynamical description of IspH to aid in the development of novel antimicrobial drugs.PLoS computational biology · 2013Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Metalloproteins (MPs) comprise one-third of all known protein structures. This diverse set of proteins contain a plethora of unique inorganic moieties capable of performing chemistry that would otherwise be impossible using only the amino acids found in nature. Most of the well-studied MPs are generally viewed as being very rigid in structure, and it is widely thought that the properties of the metal centers are primarily determined by the small fraction of amino acids that make up the local environment. Here we examine both theoretically and experimentally whether distal regions can influence the metal center in the diabetes drug target mitoNEET. We demonstrate that a loop (L2) 20 Å away from the metal center exerts allosteric control over the cluster binding domain and regulates multiple properties of the metal center. Mutagenesis of L2 results in significant shifts in the redox potential of the [2Fe-2S] cluster and orders of magnitude effects on the rate of [2Fe-2S] cluster transfer to an apo-acceptor protein. These surprising effects occur in the absence of any structural changes. An examination of the native basin dynamics of the protein using all-atom simulations shows that twisting in L2 controls scissoring in the cluster binding domain and results in perturbations to one of the cluster-coordinating histidines. These allosteric effects are in agreement with previous folding simulations that predicted L2 could communicate with residues surrounding the metal center. Our findings suggest that long-range dynamical changes in the protein backbone can have a significant effect on the functional properties of MPs.
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