Structure and substrate specificity of myo-inositol phosphatases at atomic resolution
Date
2013
Authors
Bruder, Lisza M.
Journal Title
Journal ISSN
Volume Title
Publisher
Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry
Abstract
Protein tyrosine phosphatase-like myo-inositol phosphatases (PTPLPs) follow an
ordered, sequential dephosphorylation pathway that utilizes the abundant myo-inositol-
1,2,3,4,5,6-hexakisphosphate (InsP6) to produce less-phosphorylated myo-inositol
phosphates (IPs) containing between one and five phosphoryl groups. To understand
PTPLP substrate specificity, I present multiple complex structures of Phytase A from
Selenomonas ruminantium (PhyAsr) and Mitsuokella multacida (PhyAmm; a tandem
repeat) with various IPs. From these structures I demonstrated that binding of IPs by
these enzymes is consistent with a 'lock-and-key' binding mechanism, determined binding
differences between InsP6 and less-phosphorylated IPs, and revised the existing PTPLP
substrate specificity model. As part of this work, I have produced the first PhyAmm
complex structures and demonstrated that the PhyAmm C-terminal repeat binds
substrates using identical phosphoryl binding sites as PhyAsr. Further, I have provided
evidence that differential substrate binding in the PhyAmm N- and C-terminal repeats is
due to electrostatic differences and a loop insertion causing steric clashes.
Description
x, 73 leaves : ill. (chiefly col.) ; 29 cm
Keywords
Inositol -- Research , Inositol phosphates -- Research , Dissertations, Academic