Structure-based characterization of canine-human chimeric uricases and its evolutionary implications

► Canine-human chimeric uricases were constructed to study the loss of hominoid uricase. ► The side-chains of Arg119 are crucial in maintaining the stability of active uricase. ► Inactivating mutation at codon 119 is proposed to occur first in human and great apes. ► The loss of hominoid uricase was caused by progressive multistep mutations. ► Reduction in uricase activity has been an evolutionary tendency in all mammals.