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Structural and Evolutionary Relationships
among Protein Tyrosine Phosphatase Domains
Jannik N. Andersen, Ole H. Mortensen, Günther H.
Peters Paul G. Drake,
Lars F. Iversen, Ole Hvilsted Olsen, Peter Gildsig Jansen,
Henrik S.
Andersen, Nicholas K. Tonks and Niels Peter H. Moller.
Novo Nordisk, Denmark; Dept. of
Chemistry, Technical University of Denmark
Cold
Spring Harbor Laboratory, New York, USA.
Files in this section support our analyses published in
Molecular & Cellular Biology (2001, Vol 21, p7117-7136) and Methods
(2004 in press).
To date, X-ray crystallographic structures are available for several different PTPs including
the non-transmembrane enzymes (PTP1B, TCPTP, Yop51, SHP1 and SHP2) and transmembrane receptor-like PTPs (RPTPμ, RPTPα and LAR). In addition, an impressive number of structures of PTP domains and mutant enzymes have been determined with peptide substrates or inhibitors bound in their active site.
Here, we catalog these Protein Data
Bank (pdb) files to summarize the different conformational
states that have been captured for these enzymes by X-ray crystallography.
The structures include the native ‘open’ conformation of the
enzyme, the ‘closed’ form induced upon substrate binding, the
reversible oxidized form, and so forth.
Furthermore, we summarize the proposed
roles of conserved residues and define PTP motifs in terms
of their location in the tertiary structure and, where relevant,
their catalytic function.
Finally, we superimpose divergent PTP domains to visualize their
structural features and provide molecular graphics files. The
conserved PTP fold allows evaluation of alignment information
(i.e. sequence variation and conservation) in 3D space and we
explore three different methods to project sequence alignment
information onto protein structure: Cα-regiovariation
score analysis, ProtSkin
and ConSurf.
Our structure function-analyses also identify areas in the PTP protein family
that are less well conserved and therefore might indicate a specialized
function.
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