Abstract
The OdhI protein is key regulator of the TCA cycle in Corynebacterium glutamicum. This highly conserved protein is found in GC rich Gram-positive bacteria (e.g., the pathogenic Mycobacterium tuberculosis). The unphosphorylated form of OdhI inhibits the OdhA protein, a key enzyme of the TCA cycle, whereas the phosphorylated form is inactive. OdhI is predicted to be mainly a single FHA domain, a module that mediates protein-protein interaction through binding of phosphothreonine peptides, with a disordered N-terminal extension substrate of the serine/threonine protein kinases. In this study, we solved the solution structure of the unphosphorylated and phosphorylated isoforms of the protein. We observed a major conformational change between the two forms characterized by the binding of the phosphorylated N-terminal part of the protein to its own FHA domain, consequently inhibiting it. This structural observation corresponds to a new autoinhibition mechanism described for a FHA domain protein.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Binding Sites / genetics
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Corynebacterium glutamicum / enzymology
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Corynebacterium glutamicum / genetics
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Corynebacterium glutamicum / metabolism
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Enzyme Inhibitors / metabolism*
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Ketoglutarate Dehydrogenase Complex / antagonists & inhibitors*
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Models, Biological
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Models, Molecular
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Molecular Sequence Data
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Molecular Weight
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Mycobacterium tuberculosis / enzymology
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Mycobacterium tuberculosis / genetics
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Mycobacterium tuberculosis / metabolism
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Peptides / chemistry
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Peptides / metabolism
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Phosphorylation
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Phosphothreonine / chemistry
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Phosphothreonine / metabolism
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Protein Binding / genetics
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Protein Conformation
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Protein Structure, Tertiary / genetics
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Sequence Homology, Amino Acid
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Substrate Specificity / genetics
Substances
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Bacterial Proteins
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Enzyme Inhibitors
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Peptides
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Phosphothreonine
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Ketoglutarate Dehydrogenase Complex
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Protein Serine-Threonine Kinases