Angiotensin II-forming activity in a reconstructed ancestral chymase.
The current model of serine protease diversity theorizes that the earliest protease molecules were simple digestive enzymes that gained complex regulatory functions and restricted substrate specificities through evolution. Among the chymase group of serine proteases are enzymes that convert angiotensin I to angiotensin II, as well as others that simply degrade angiotensins. An ancestral chymase reconstructed with the use of phylogenetic inference, total gene synthesis, and protein expression had efficient and specific angiotensin II-forming activity (turnover number, about 700 per second). Thus, angiotensin II-forming activity is the more primitive state for chymases, and the loss of such activity occurred later in the evolution of some of these serine proteases.
Chandrasekharan
U M
UM
Department of Molecular Cardiology, Cleveland Clinic Foundation, OH 44195, USA.
Sanker
S
S
Glynias
M J
MJ
Karnik
S S
SS
Husain
A
A
D000595:Amino Acid Sequence; D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D053818:Chymases; D019143:Evolution, Molecular; D005813:Genes, Synthetic; D006801:Humans; D008969:Molecular Sequence Data; D051381:Rats; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D000809:Angiotensins; D000804:Angiotensin II; D000803:Angiotensin I; D012697:Serine Endopeptidases; D053818:Chymases