Structural Model of Human Glucokinase in Complex With Glucose and ATP: Implications for the Mutants That Cause Hypo- and Hyperglycemia

摘要

Mutations in human glucokinase are implicate in the development of diabetes and hypoglycemia. Human glucokinase shares 54/100 identical amino acid residues with human brain hexokinase I. This similarity was used to model the structure of glucokinase b analogy to the crystal structure of rain hexokinase. Gluco- kinase was modeled with both its substrates, glucose and MgATP, to understand the effect of mutations. The glucose is predicted to form hydrogen bond interac- tions with the side chains of glucokinase residues Thr 168, Lys 169, As 204, Asp 205, Asn 231, and Glu 290, similar to those observed for brain hexokinase I.