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 angioten...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1996-01, Vol.271 (5248), p.502-505
Main Authors: Chandrasekharan, Unnikrishnan M., Sanker, Subramaniam, Glynias, Manuel J., Karnik, Sadashiva S., Husain, Ahsan
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Angiotensin I - metabolism
Angiotensin II - metabolism
Angiotensins - metabolism
Animal social behavior
Animals
Binding Sites
Biological and medical sciences
Biological evolution
Chemical evolution
Chymases
Enzymes
Evolution
Evolution, Molecular
Fundamental and applied biological sciences. Psychology
Genes, Synthetic
Genetics of eukaryotes. Biological and molecular evolution
Hormones
Humans
Kinetics
Leukocytes
Mast cells
Molecular evolution
Molecular Sequence Data
Parsimony
Phylogenetics
Proteases
Rats
Serine Endopeptidases - chemistry
Serine Endopeptidases - genetics
Serine Endopeptidases - metabolism
Substrate Specificity
Topology
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.271.5248.502