3W0L

The crystal structure of Xenopus Glucokinase and Glucokinase Regulatory Protein complex

Summary for 3W0L

• Entry DOI: 10.2210/pdb3w0l/pdb
• Descriptor: Glucokinase, Glucokinase regulatory protein, SULFATE ION, ... (6 entities in total)
• Functional Keywords: aba sandwich, typical hexokanse fold, kinase, sugar binding, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 4
• Total formula weight: 240865.78

Authors

Choi, J.M.,Seo, M.H.,Kyeong, H.H.,Kim, E.,Kim, H.S. (deposition date: 2012-10-31, release date: 2013-07-17, Last modification date: 2023-11-08)

Primary citation

Choi, J.M.,Seo, M.H.,Kyeong, H.H.,Kim, E.,Kim, H.S.
Molecular basis for the role of glucokinase regulatory protein as the allosteric switch for glucokinase
Proc.Natl.Acad.Sci.USA, 110:10171-10176, 2013

PubMed Abstract: 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.

PubMed: 23733961
DOI: 10.1073/pnas.1300457110

Experimental method

X-RAY DIFFRACTION (2.92 Å)