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 (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 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.