We purified pancreatic deoxyribonucleases I (DNases I) from three snakes, Elaphe quadrivirgata, Elaphe climacophora and Agkistrodon blomhoffii, and cloned their cDNAs. Each mature snake DNase I protein comprised 262 @entity1522 . Wild-type snake DNases I with Leu130 were more thermally unstable than wild-type @entity1 and avian DNases I with Ile130. After substitution of @entity70462 , the thermal stabilities of the snake enzymes were higher than those of their wild-type counterparts and similar to @entity1 wild-type enzyme levels. Conversely, substituting @entity70463 of @entity1 DNases I made them more thermally unstable than their wild-type counterparts. Therefore, a single @entity535 substitution, @entity70462 , might be involved in an evolutionally critical change in the thermal stabilities of vertebrate DNases I. Amphibian DNases I have a Ser205 insertion in a @entity141 -binding site of @entity1 and avian enzymes that reduces their thermal stabilities [Takeshita, H., Yasuda, T., Iida, R., Nakajima, T., Mori, S., Mogi, K., Kaneko, Y. _ Kishi, K. (2001) Biochem. J.357, 473-480]. Thus, it is plausible that the thermally stable wild-type DNases I of the higher vertebrates, such as mammals and birds, have been generated by a single @entity70462 substitution of reptilian enzymes through molecular evolution following Ser205 deletion from amphibian enzymes. This mechanism may reflect one of the evolutionary changes from cold-blooded to warm-blooded vertebrates.

A single @entity535 substitution of XXXX in snake DNases I contributes to the acquisition of thermal stability.

@entity1 :: ('9606', 'Species') :: ['mammalian'] @entity1522 :: ('CHEBI:33709', 'Chemical') :: ['amino acids'] @entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid'] @entity70463 :: ('p|SUB|I|130|L', 'ProteinMutation') :: ['Ile130Leu'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity70462 :: ('p|SUB|L|130|I', 'ProteinMutation') :: ['Leu130Ile']
@entity70462 :: (p|SUB|L|130|I,ProteinMutation) :: ['Leu130Ile']
