Structural and mutational analyses of decarboxylated osteocalcin provide insight into its adiponectin‐inducing activity.

An acidic environment in bone is essential for bone metabolism and the production of decarboxylated osteocalcin, which functions as a regulatory hormone of glucose metabolism. Here, we describe the high‐resolution X‐ray crystal structure of decarboxylated osteocalcin under acidic conditions. Decarboxylated osteocalcin at pH 2.0 retains the α‐helix structure of native osteocalcin with three γ‐carboxyglutamic acid residues at neutral pH. This implies that decarboxylated osteocalcin is stable under an acidic environment in bone. In addition, site‐directed mutagenesis revealed that Glu17 and Glu21 are important for the adiponectin‐inducing activity of decarboxylated osteocalcin. These findings suggest that the receptor of decarboxylated osteocalcin responds to the negative charge in helix 1 of osteocalcin. [ABSTRACT FROM AUTHOR]