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,
Andersen, Nicholas K. Tonks and Niels Peter H. Moller.
Novo Nordisk, Denmark; Dept. of
Chemistry, Technical University of Denmark
Spring Harbor Laboratory, New York, USA.
Files in this section support our analyses published
Molecular & Cellular Biology (2001, Vol 21, p7117-7136)
(2005, Vol 35, p90-114).
To date, X-ray crystallographic structures are available for
several different PTPs including the non-transmembrane enzymes
(PTP1B, TCPTP, Yop51, PTPSL, SHP1 and SHP2) and transmembrane
receptor-like PTPs (RPTPμ, RPTPα, CD45and 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
Our structure function-analyses also identify areas in the PTP protein family
that are less well conserved and therefore might indicate a specialized