Campylobacter jejuniadenosine triphosphate phosphoribosyltransferase is an active hexamer that is allosterically controlled by the twisting of a regulatory tail
| Autor: | Gerd Mittelstädt, Santosh Panjikar, Ali Reza Nazmi, Gert-Jan Moggré, Emily J. Parker |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adenosine monophosphate 030102 biochemistry & molecular biology biology Stereochemistry Allosteric regulation food and beverages Random hexamer biology.organism_classification Biochemistry Campylobacter jejuni ATP phosphoribosyltransferase 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry biology.protein Phosphoribosyltransferase Molecular Biology Adenosine triphosphate Histidine |
| Zdroj: | Protein Science. 25:1492-1506 |
| ISSN: | 0961-8368 |
| Popis: | Adenosine triphosphate phosphoribosyltransferase (ATP-PRT) catalyzes the first committed step of the histidine biosynthesis in plants and microorganisms. Here, we present the functional and structural characterization of the ATP-PRT from the pathogenic e-proteobacteria Campylobacter jejuni (CjeATP-PRT). This enzyme is a member of the long form (HisGL ) ATP-PRT and is allosterically inhibited by histidine, which binds to a remote regulatory domain, and competitively inhibited by AMP. In the crystalline form, CjeATP-PRT was found to adopt two distinctly different hexameric conformations, with an open homohexameric structure observed in the presence of substrate ATP, and a more compact closed form present when inhibitor histidine is bound. CjeATP-PRT was observed to adopt only a hexameric quaternary structure in solution, contradicting previous hypotheses favoring an allosteric mechanism driven by an oligomer equilibrium. Instead, this study supports the conclusion that the ATP-PRT long form hexamer is the active species; the tightening of this structure in response to remote histidine binding results in an inhibited enzyme. |
| Databáze: | OpenAIRE |
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