A dimeric catalytic core relates the short and long forms of ATP-phosphoribosyltransferase
| Autor: | Gerd Mittelstädt, Emma K. Livingstone, Wanting Jiao, Emily J. Parker, Gert-Jan Moggré, Ali Reza Nazmi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Models
Molecular Protein Conformation alpha-Helical 0301 basic medicine Stereochemistry Amino Acid Motifs Genetic Vectors Allosteric regulation Gene Expression Crystallography X-Ray Biochemistry Substrate Specificity Campylobacter jejuni 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate Protein structure Allosteric Regulation Bacterial Proteins Catalytic Domain Escherichia coli Transferase Histidine Protein Interaction Domains and Motifs Cloning Molecular Molecular Biology 030102 biochemistry & molecular biology biology Chemistry food and beverages Active site Cell Biology ATP Phosphoribosyltransferase Adenosine Monophosphate Recombinant Proteins ATP phosphoribosyltransferase Isoenzymes Kinetics 030104 developmental biology biology.protein Phosphoribosyltransferase Protein Conformation beta-Strand Protein Multimerization Adenosine triphosphate Protein Binding |
| Zdroj: | Biochemical Journal. 475:247-260 |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | Adenosine triphosphate (ATP) phosphoribosyltransferase (ATP-PRT) catalyses the first committed step of histidine biosynthesis in plants and microorganisms. Two forms of ATP-PRT have been reported, which differ in their molecular architecture and mechanism of allosteric regulation. The short-form ATP-PRT is a hetero-octamer, with four HisG chains that comprise only the catalytic domains and four separate chains of HisZ required for allosteric regulation by histidine. The long-form ATP-PRT is homo-hexameric, with each chain comprising two catalytic domains and a covalently linked regulatory domain that binds histidine as an allosteric inhibitor. Here, we describe a truncated long-form ATP-PRT from Campylobacter jejuni devoid of its regulatory domain (CjeATP-PRTcore). Results showed that CjeATP-PRTcore is dimeric, exhibits attenuated catalytic activity, and is insensitive to histidine, indicating that the covalently linked regulatory domain plays a role in both catalysis and regulation. Crystal structures were obtained for CjeATP-PRTcore in complex with both substrates, and for the first time, the complete product of the reaction. These structures reveal the key features of the active site and provide insights into how substrates move into position during catalysis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|