Heme-Edge Residues Modulate Signal Transduction within a Bifunctional Homo-Dimeric Sensor Protein
| Autor: | Dayna C Patterson, Emily E. Weinert, Yilin Liu, Neela H. Yennawar, James R. Kincaid, Sayan Das, Jean Paul Armache |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Hemeproteins
Models Molecular Protein Conformation alpha-Helical Static Electricity Population Gene Expression Heme 010402 general chemistry 01 natural sciences Biochemistry Substrate Specificity Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Protein structure Bacterial Proteins Guanosine monophosphate Escherichia coli Protein Interaction Domains and Motifs Phosphofructokinase 2 Amino Acid Sequence DCPG Enzyme kinetics education Cyclic GMP 030304 developmental biology 0303 health sciences education.field_of_study Binding Sites Sequence Homology Amino Acid Phosphoric Diester Hydrolases Escherichia coli Proteins Recombinant Proteins 0104 chemical sciences Oxygen Kinetics Amino Acid Substitution chemistry Biophysics Protein Conformation beta-Strand Phosphorus-Oxygen Lyases Protein Multimerization Signal transduction Paenibacillus Sequence Alignment Protein Binding Signal Transduction |
| Zdroj: | Biochemistry. 60:3801-3812 |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | Bifunctional enzymes, which contain two domains with opposing enzymatic activities, are widely distributed in bacteria, but the regulatory mechanism(s) that prevent futile cycling are still poorly understood. The recently described bifunctional enzyme, DcpG, exhibits unusual heme properties and is surprisingly able to differentially regulate its two cyclic dimeric guanosine monophosphate (c-di-GMP) metabolic domains in response to heme gaseous ligands. Mutagenesis of heme-edge residues was used to probe the heme pocket and resulted in decreased O2 dissociation kinetics, identifying roles for these residues in modulating DcpG gas sensing. In addition, the resonance Raman spectra of the DcpG wild type and heme-edge mutants revealed that the mutations alter the heme electrostatic environment, vinyl group conformations, and spin state population. Using small-angle X-ray scattering and negative stain electron microscopy, the heme-edge mutations were demonstrated to cause changes to the protein conformation, which resulted in altered signaling transduction and enzyme kinetics. These findings provide insights into molecular interactions that regulate DcpG gas sensing as well as mechanisms that have evolved to control multidomain bacterial signaling proteins. |
| Databáze: | OpenAIRE |
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