Structure of a pH-Sensing Mycobacterial Adenylyl Cyclase Holoenzyme

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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2005-05, Vol.308 (5724), p.1020-1023
Main Authors: Tews, Ivo, Findeisen, Felix, Sinning, Irmgard, Schultz, Anita, Schultz, Joachim E, Linder, Jůrgen U
Format: Article
Language:English
Subjects:
Active sites
Adenosine
Adenosine Triphosphate - metabolism
Adenylate cyclase
Adenylyl cyclase
Adenylyl Cyclase Inhibitors
Adenylyl Cyclases - chemistry
Adenylyl Cyclases - genetics
Adenylyl Cyclases - metabolism
Amino Acid Sequence
Amino acids
Atoms
Bacteria
Bacterial Proteins - antagonists & inhibitors
Bacterial Proteins - chemistry
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Biological and medical sciences
Catalysis
Catalytic Domain
Chemical Phenomena
Chemistry, Physical
Crystallography, X-Ray
Crystals
Dimerization
Dimers
Drug regulation
Enzymes
Fundamental and applied biological sciences. Psychology
Genomes
Growth, nutrition, metabolism, transports, enzymes. Molecular biology
Holoenzymes - chemistry
Holoenzymes - metabolism
Hydrogen Bonding
Hydrogen-Ion Concentration
Individualized Instruction
Microbiology
Models, Molecular
Molecular Sequence Data
Monomers
Mutation
Mycobacteria
Mycobacterium
Mycobacterium tuberculosis - enzymology
Mycology
Protein Conformation
Protein Structure, Quaternary
Protein Structure, Secondary
Protein Structure, Tertiary
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Description
Summary: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° 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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1107642