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A despecialization step underlying evolution of a family of serine proteases

Wouters, Merridee A., Liu, Ke, Riek, Peter and Husain, Ahsan 2003, A despecialization step underlying evolution of a family of serine proteases, Molecular cell, vol. 12, no. 2, pp. 343-354, doi: 10.1016/S1097-2765(03)00308-3.

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Title A despecialization step underlying evolution of a family of serine proteases
Author(s) Wouters, Merridee A.
Liu, Ke
Riek, Peter
Husain, Ahsan
Journal name Molecular cell
Volume number 12
Issue number 2
Start page 343
End page 354
Total pages 12
Publisher Cell Press
Place of publication Cambridge, Mass.
Publication date 2003-08-01
ISSN 1097-2765
1097-4164
Keyword(s) alpha chymase
beta chymase
cathepsin g protease
chymase
granzyme B
serine proteinase
unclassified drug
Summary In the trypsin superfamily of serine proteases, non-trypsin-like primary specificities have arisen in only two monophyletic descendent subbranches. We have recreated an ancestor to one of these subbranches (granzyme) using phylogenetic inference, gene synthesis, and protein expression. This ancestor has two unusual properties. First, it has broad primary specificity encompassing the entire repertoire of novel primary specificities found in its descendents. Second, unlike extant members that have narrow primary specificities, the ancestor exhibits tolerance to mutational changes in primary specificity-conferring residues—that is, structural plasticity. Molecular modeling and mutagenesis studies indicate that these unusual properties are due to a particularly wide substrate binding pocket. These two crucial properties of the ancestor not only distinguish it from its extant descendents but also from the trypsin-like proteases that preceded it. This indicates that a despecialization step, characterized by broad specificity and structural plasticity, underlies evolution of new primary specificities in this protease superfamily.
Language eng
DOI 10.1016/S1097-2765(03)00308-3
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2003, Elsevier
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30038994

Document type: Journal Article
Collections: School of Life and Environmental Sciences
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.