Molecular basis for the role of glucokinase regulatory protein as the allosteric switch for glucokinase
| Autor: | Eun Kyung Kim, Moon-Hyeong Seo, Hyun-Ho Kyeong, Hak-Sung Kim, Jung Min Choi |
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| Rok vydání: | 2013 |
| Předmět: |
Blood Glucose
Protein Conformation Allosteric regulation Plasma protein binding Xenopus Proteins Crystallography X-Ray Structure-Activity Relationship Xenopus laevis chemistry.chemical_compound Protein structure Allosteric Regulation Glucokinase Animals Humans Glucose homeostasis Adaptor Proteins Signal Transducing Hexokinase Multidisciplinary biology Glucokinase regulatory protein Intracellular Signaling Peptides and Proteins Biological Sciences Cell biology Diabetes Mellitus Type 2 Liver Allosteric enzyme chemistry Biochemistry biology.protein Carrier Proteins Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences. 110:10171-10176 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1300457110 |
| Popis: | Glucokinase (GK) is a monomeric allosteric enzyme and plays a pivotal role in blood glucose homeostasis. GK is regulated by GK regulatory protein (GKRP), and indirectly by allosteric effectors of GKRP. Despite the critical roles of GK and GKRP, the molecular basis for the allosteric regulation mechanism of GK by GKRP remains unclear. We determined the crystal structure of Xenopus GK and GKRP complex in the presence of fructose-6-phosphate at 2.9 Å. GKRP binds to a super-open conformation of GK mainly through hydrophobic interaction, inhibiting the GK activity by locking a small domain of GK. We demonstrate the molecular mechanism for the modulation of GK activity by allosteric effectors of GKRP. Importantly, GKRP releases GK in a sigmoidal manner in response to glucose concentration by restricting a structural rearrangement of the GK small domain via a single ion pair. We find that GKRP acts as an allosteric switch for GK in blood glucose control by the liver. |
| Databáze: | OpenAIRE |
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