Abstract
Class III adenylyl cyclases contain catalytic and regulatory domains, yet structural insight into their interactions is missing. We show that the mycobacterial adenylyl cyclase Rv1264 is rendered a pH sensor by its N-terminal domain. In the structure of the inhibited state, catalytic and regulatory domains share a large interface involving catalytic residues. In the structure of the active state, the two catalytic domains rotate by 55 degrees to form two catalytic sites at their interface. Two alpha helices serve as molecular switches. Mutagenesis is consistent with a regulatory role of the structural transition, and we suggest that the transition is regulated by pH.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / metabolism
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Adenylyl Cyclase Inhibitors
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Adenylyl Cyclases / chemistry*
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Adenylyl Cyclases / genetics
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Adenylyl Cyclases / metabolism*
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Amino Acid Sequence
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Bacterial Proteins / antagonists & inhibitors
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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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Catalytic Domain
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Chemical Phenomena
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Chemistry, Physical
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Crystallography, X-Ray
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Dimerization
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Holoenzymes / chemistry
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Holoenzymes / metabolism
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Hydrogen Bonding
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Hydrogen-Ion Concentration
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Mycobacterium tuberculosis / enzymology*
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Protein Conformation
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Protein Structure, Quaternary
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Protein Structure, Secondary
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Protein Structure, Tertiary
Substances
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Adenylyl Cyclase Inhibitors
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Bacterial Proteins
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Holoenzymes
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Adenosine Triphosphate
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Adenylyl Cyclases
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Rv1264 protein, Mycobacterium tuberculosis